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Astaxanthin improves muscle lipid metabolism in exercise via inhibitory effect of oxidative CPT I modification

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Abstract

Intracellular redox balance may affect nutrient metabolism in skeletal muscle. Astaxanthin, a carotenoid contained in various natural foods, exerts high antioxidative capacity in the skeletal muscles. The present study investigated the effect of astaxanthin on muscle lipid metabolism in exercise. ICR mice (8 weeks old) were divided into four different groups: sedentary, sedentary treated with astaxanthin, running exercise, and exercise treated with astaxanthin. After 4 weeks of treatment, exercise groups performed treadmill running. Astaxanthin increased fat utilization during exercise compared with mice on a normal diet with prolongation of the running time to exhaustion. Colocalization of fatty acid translocase with carnitine palmitoyltransferase I (CPT I) in skeletal muscle was increased by astaxanthin. We also found that hexanoyl-lysine modification of CPT I was increased by exercise, while astaxanthin prevented this increase. In additional experiment, we found that astaxanthin treatment accelerated the decrease of body fat accumulation with exercise training. Our results suggested that astaxanthin promoted lipid metabolism rather than glucose utilization during exercise via CPT I activation, which led to improvement of endurance and efficient reduction of adipose tissue with training.

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... Many other studies have documented that dietary consumption of ASX can prevent or reduce the risk of various medical conditions in humans and animals [25]. In addition, long-term supplementation of ASX in mice also delays time to exhaustion during exercise [26][27][28][29][30]. Hence, ASX is considered a potent antioxidant utilized as a nutritional supplement for physical exercise participants [31]. ...
... The mice in the three SA groups were orally treated with 0.1 mL of the mixture of ASX and olive oil by gavage and participated in a supplementation regime with dosages of ASX 5 mg/kg Body Weight (BW; SA5), 15 mg/kg BW (SA15), and 30 mg/kg BW (SA30), respectively. The supplemented quantity of ASX was based on published work [26,28]. However, some modifications were made for evaluating ASX concentrations in larger quantities during this experiment. ...
... Supplementation of three different dosages of ASX significantly decreased plasma CK, compared with the swimming control group. Other studies provide evidence that ASX can decrease CK activity in mice [26,57] or in humans [55,58]. Nevertheless, Richard et al., reported that supplementation of 4 mg/day ASX in humans did not favorably affect CK values associated with skeletal muscle injury following eccentric resistance strength training [59]. ...
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Exercise-induced reactive oxygen and nitrogen species are increasingly considered as beneficial health promotion. Astaxanthin (ASX) has been recognized as a potent antioxidant suitable for human ingestion. We investigated whether ASX administration suppressed antioxidant enzyme activity in moderate-intensity exercise. Seven-week-old male C57BL/6 mice (n = 8/group) were treated with ASX (5, 15, and 30 mg/kg BW) combined with 45 min/day moderate-intensity swimming training for four weeks. Results showed that the mice administrated with 15 and 30 mg/kg of ASX decreased glutathione peroxidase, catalase, malondialdehyde, and creatine kinase levels in plasma or muscle, compared with the swimming control group. Beyond that, these two (15 and 30 mg/kg BW) dosages of ASX downregulated gastrocnemius muscle erythroid 2p45 (NF-E2)-related factor 2 (Nrf2). Meanwhile, mRNA of Nrf2 and Nrf2-dependent enzymes in mice heart were also downregulated in the ASX-treated groups. However, the mice treated with 15 or 30 mg/kg ASX had increased constitutive nitric oxidase synthase and superoxide dismutase activity, compared with the swimming and sedentary control groups. Our findings indicate that high-dose administration of astaxanthin can blunt antioxidant enzyme activity and downregulate transcription of Nrf2 and Nrf2-dependent enzymes along with attenuating plasma and muscle MDA.
... Benefits of AX supplementation on exercise performance have been reported in mice and humans. In mice, AX supplementation increased exercise capacity and fat oxidation during both swimming and treadmill exercise to exhaustion (Aoi et al., 2008;Ikeuchi et al., 2006). The increased time to exhaustion was related to increased lipid oxidation, reduced blood lactate, and reduced liver and muscle glycogen utilization (Aoi et al., 2008;Ikeuchi et al., 2006;Liu et al., 2014). ...
... In mice, AX supplementation increased exercise capacity and fat oxidation during both swimming and treadmill exercise to exhaustion (Aoi et al., 2008;Ikeuchi et al., 2006). The increased time to exhaustion was related to increased lipid oxidation, reduced blood lactate, and reduced liver and muscle glycogen utilization (Aoi et al., 2008;Ikeuchi et al., 2006;Liu et al., 2014). The effect of AX on muscle metabolism and performance is less clear in humans, with some showing a reduction in injury markers (Djordjevic et al., 2012) but not others (Bloomer et al., 2005), or benefits in strength (Malmsten & Lignell, 2008) in healthy male athletes. ...
... It is important to point out some potential pathways published in the literature for future clinical trials. (Aoi et al., 2008) reported that AX improved fat oxidation in mice through increased co-immunoprecipitation of fatty acyl transferase (FAT/CD36) with carnitine palmitoyltransferase I (CPTI), and AX reduced oxidative stress-induced modification of CPTI by hexanoyl-lysine adduct (HEL). In contrast, other antioxidant, such as vitamin C and E, have mixed results: either enhancing or interfering with exercise adaptation (Gomez-Cabrera et al., 2008;Peternelj & Coombes, 2011). ...
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Endurance training (ET) is recommended for the elderly to improve metabolic health and aerobic capacity. However, ET‐induced adaptations may be suboptimal due to oxidative stress and exaggerated inflammatory response to ET. The natural antioxidant and anti‐inflammatory dietary supplement astaxanthin (AX) has been found to increase endurance performance among young athletes, but limited investigations have focused on the elderly. We tested a formulation of AX in combination with ET in healthy older adults (65–82 years) to determine if AX improves metabolic adaptations with ET, and if AX effects are sex‐dependent. Forty‐two subjects were randomized to either placebo (PL) or AX during 3 months of ET. Specific muscle endurance was measured in ankle dorsiflexors. Whole body exercise endurance and fat oxidation (FATox) was assessed with a graded exercise test (GXT) in conjunction with indirect calorimetry. Results: ET led to improved specific muscle endurance only in the AX group (Pre 353 ± 26 vs. Post 472 ± 41 contractions), and submaximal GXT duration improved in both groups (PL 40.8 ± 9.1% and AX 41.1 ± 6.3%). The increase in FATox at lower intensity after ET was greater in AX (PL 0.23 ± 0.15 g vs. AX 0.76 ± 0.18 g) and was associated with reduced carbohydrate oxidation and increased exercise efficiency in males but not in females. Astaxanthin combined with endurance training promoted fat oxidation compared to training alone. Astaxanthin led to carbohydrate sparing and improved exercise efficiency especially in older males.
... In terms of exercise effects, astaxanthin has shown positive results for reducing lactic acid accumulation, increasing fat oxidation/metabolism, and improving endurance performance with most studies demonstrating benefits [18][19][20][21][22][23][24][25][26][27][28]. Many of these effects may be attributed to a hypothesized mitochondrial-centric mechanism, which could improve energy and redox cellular metabolism (e.g. via Nrf2-ARE pathway activation). ...
... Astaxanthin (AX) is a naturally occurring carotenoid, synthesized primarily by marine microalgae, with powerful antioxidant and anti-inflammatory properties. In mammals, dietary AX accumulates in muscle, where it attenuates muscle damage and inhibits peroxidation of DNA and lipids due to prolonged exercise [18][19][20]. In addition, AX has been identified as a nutrient that may strongly stimulate fat oxidation during exercise. ...
... In addition, AX has been identified as a nutrient that may strongly stimulate fat oxidation during exercise. AX supplementation of mice (4-5 weeks with 6-30mg/kg BW) improves fat utilization and increases swimming and treadmill running time to exhaustion [20,21]. These effects were theorized to be attributable to an improved mitochondrial capacity for fatty acyl-CoA uptake via an improvement in carnitine palmitoyltransferase 1 (CPT1) function, subsequent to inhibition of oxidative damage to the mitochondrial membrane. ...
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Objective: Marine microalgae is the predominant source of natural astaxanthin (NAX), a red-orange carotenoid with powerful antioxidant and anti-inflammatory properties. Previous studies suggest that NAX supplementation improves antioxidant capacity and reduces oxidative stress, while also enhancing fat utilization, exercise endurance, cardiovascular function, and neurological parameters. The purpose of this study was to assess the effects of NAX on the psychophysiological “heart-brain-axis” while nutrition (astaxanthin) may impact physiology (cardiovascular function) and psychology (mood state) in a coordinated manner. Methods: Using a double-blind parallel design, 28 healthy subjects (male=14, female=14, age=42) were supplemented for 8 weeks with NAX (12mg/day Haematococcus pluvialis algal extract) or a matching placebo. Before and after supplementation, subjects performed a cardiovascular stress test (VO2max) and completed a validated Profile of Mood States (POMS) survey to assess global mood state (GM) and related subscales: Vigor (V), Tension (T), Depression (D), Anger (A), Fatigue (F), and Confusion (C). Results: Subjects in the NAX group showed a significant ~10% lower average heart rate at submaximal exercise intensities compared to those in the placebo group (aerobic threshold, AeT; NAX 130+17 v. PL 145+14; and anaerobic threshold, AT; NAX 139+20 v. PL 154+11, p<0.05). Significant improvements were found in the NAX group for both positive mood state parameters: GM (+11%, p<0.05) & V (+5%, NS); and negative mood state parameters: T (-20%, NS), D (-57%, p<0.05), A (-12%, NS), F (-36%, p<0.05), and C (-28%, NS). Conclusions: NAX supplementation lowered average heart rate at submaximal endurance intensities (suggesting a “physical” heart benefit) and improved mood state parameters (suggesting a “mental” brain benefit). While previous studies have shown NAX supplementation to improve parameters associated with heart health (antioxidant, fat oxidation, endurance) and brain health (neuro-inflammation, cognition, antidepressant/anxiolytic), these results suggest that natural astaxanthin supplementation supports the psychophysiological “heart-brain-axis” with simultaneous improvements in both physical and mental wellness. Keywords: Antioxidant; Carotenoid; Cardiovascular; Mood State; Mental Wellness
... PGC-1α was significantly elevated in skeletal muscle samples following astaxanthin intake, and cytochrome C levels were also increased in mice [90]. Moreover, the levels of plasma fatty acids were decreased after exercise in the astaxanthin-fed mice [90], and the fat utilization of skeletal muscle was improved during exercise in a treadmill running model by activation of carnitine palmitoyltransferase I [91]. Interestingly, PGC-1α increases the level of GLUT4 and has multiple roles in the pathogenesis of type-2 diabetes mellitus [92], but the effects of astaxanthin on the PGC-1α/GLUT4 pathway have not been studied. ...
... Four weeks of astaxanthin treatment in mice prolonged the running to exhaustion. During exercise, astaxanthin administration facilitated lipid metabolism instead of glucose utilization, which improved the endurance and reduced adipose tissue [91]. The same group showed the effect of astaxanthin on ROS-targeted proteins involved in skeletal muscle metabolism during exercise. ...
... It has been proved that astaxanthincontaining diet modified the expression level of PGC-1α, thereby inducing the mitochondrial biogenesis in vivo [90]. It was shown also that the prolonged supplementation has not modified the lipid oxidation in order to spare glycogen stores during training, as it already proved in animal studies, which can be due to the increased fitness levels of the inspected subjects [91]. Krill oil treatment also activated the mTORC1 signaling pathway as it was shown in C2C12 myoblasts; however, in young, untrained, healthy individuals, 3 g of krill oil (0.5 g astaxanthin content) administration during 8 weeks did not elevate significantly the muscle force in resistance exercise [117]. ...
Article
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Oxidative stress is characterized by an imbalance between prooxidant and antioxidant species, leading to macromolecular damage and disruption of redox signaling and cellular control. It is a hallmark of various diseases including metabolic syndrome, chronic fatigue syndrome, neurodegenerative, cardiovascular, inflammatory, and age-related diseases. Several mitochondrial defects have been considered to contribute to the development of oxidative stress and known as the major mediators of the aging process and subsequent age-associated diseases. Thus, mitochondrial-targeted antioxidants should prevent or slow down these processes and prolong longevity. This is the reason why antioxidant treatments are extensively studied and newer and newer compounds with such an effect appear. Astaxanthin, a xanthophyll carotenoid, is the most abundant carotenoid in marine organisms and is one of the most powerful natural compounds with remarkable antioxidant activity. Here, we summarize its antioxidant targets, effects, and benefits in diseases and with aging.
... With respect to exercise effects, astaxanthin has shown positive results for reducing lactic acid accumulation, increasing fat oxidation, and improving endurance performance with most studies demonstrating benefits [17][18][19][20][21][22][23][24]. ...
... In addition, AX has been identified as a nutrient that may strongly stimulate fat oxidation during exercise. AX supplementation of mice (4 -5 weeks with 6 -30 mg/kg BW) improves fat utilization and increases swimming and treadmill running time to exhaustion [19,20]. These effects were theorized to be attributable to an improved mitochondrial capacity for fatty acyl-CoA uptake via an improvement in carnitine palmitoyltransferase 1 (CPT1) function, subsequent to inhibition of oxidative damage to the mitochondrial membrane. ...
... Previous studies of NAX administration in animal models has shown a decrease in exercise-induced damage to skeletal and cardiac muscle, as well as an increase in redox balance, fat oxidation and time to exhaustion during exercise [17][18][19][20]22]. Some positive rodent studies have administered NAX at fairly high dosages of 6 -30 mg/kg [18][19][20][21], while others have used lower amounts (1 mg/kg) to delay physical exhaustion and improve redox balance [22] relatively higher than the amounts of NAX supplemented in human trials (2 -20 mg/ day). ...
... Among papers on animal research, there are ten rodent model studies relevant to the purpose of this review ( Table 1). Five of these evaluated the effects of ASX supplementation on exercise performance, and all five showed positive effects [33][34][35][36][37]. Another five studies evaluated the effects of ASX on health-related parameters [38][39][40][41][42], of which two were related to cognitive function [41,42]. ...
... Among all studies, only three were able to investigate the interaction between exercise and ASX supplementation [34,39,42]. One study found additive effects on exercise performance. ...
... The synergistic effect could not be evaluated since there were no data for ASX intervention alone. The additive effect of ASX on exercise training was explained by describing the improving fat metabolism and decreasing oxidative stress [34]. A second interesting article found two distinct interaction effects (antagonistic and additive); however, there was no ASX intervention alone to measure the synergistic effect. ...
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A healthy lifestyle is essential for maintaining physical and mental health. Health promotion, with a particular emphasis on regular exercise and a healthy diet, is one of the emerging trends in healthcare. However, the way in which exercise training and nutrients from dietary intake interact with each other to promote additive, synergistic, or antagonistic effects on physiological functions leading to health promotion, and the possible underlying biomolecular mechanisms of such interactions, remain poorly understood. A healthy diet is characterized by a high intake of various bioactive compounds usually found in natural, organic, and fresh foodstuffs. Among these bioactive compounds, astaxanthin (ASX), a red carotenoid pigment especially found in seafood, has been recognized in the scientific literature as a potential nutraceutical due to its antioxidant, anti-inflammatory, and neurotrophic properties. Therefore, scientists are currently exploring whether this promising nutrient can increase the well-known benefits of exercise on health and disease prevention. Hence, the present review aimed to compile and summarize the current scientific evidence for ASX supplementation in association with exercise regimes, and evaluate the additive or synergistic effects on physiological functions and health when both interventions are combined. The new insights into the combination paradigm of exercise and nutritional supplementation raise awareness of the importance of integrative studies, particularly for future research directions in the field of health and sports nutrition science.
... Hence, lipids appear to be more protected by carotenoids than other biological molecules. Together with lipid protection, several studies have reported that carotenoids may also influence lipid metabolism (Ikeuchi, Koyama, Takahashi & Yazawa 2007;Tsukui, Konno, Hosokawa, Maeda, Sashima & Miyashita 2007;Aoi, Naito, Takanami, Ishii, Kawai, Akagiri, Kato, Osawa & Yoshikawa 2008;Woo, Jeon, Kim, Lee, Shin, Shin, Park & Choi 2010;Hu, Li, Li, Fu, Cai, Chen & Li 2012). ...
... In red porgy, dietary astaxanthin decreased total lipid in whole fish and liver; as well as palmitic acid, an important fish energy substrate (Kalinowski et al. 2011). In obese mice dietary astaxanthin (Ikeuchi et al. 2007;Aoi et al. 2008;Yazawa 2008) and dietary fucoxanthin (Woo, Jeon, Shin, Lee, Kang & Choi 2009;Woo et al. 2010;Hu et al. 2012) both reduced body weight, weight of adipose tissue, liver weight, and triglycerides and cholesterol in plasma, liver and adipose tissue. ...
... Compounds with antioxidant properties may improve lipid metabolism (RuiLi Yang, Guowei, Anlin Li, Jianling Zheng & Yonghui Shi 2006). Indeed, carotenoids influence lipid desaturation and elongation (Bell et al. 2000;Tsukui, Hosokawa & Miyashita 2008) as well as lipogenesis and b-oxidation (Ikeuchi et al. 2007;Aoi et al. 2008;Yazawa 2008;Woo et al. 2009Woo et al. , 2010Hu et al. 2012). Nevertheless, relatively few studies have been carried out evaluating this aspect in fish. ...
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A 24-week feeding trial was conducted to study the possible effect of dietary canthaxanthin on red porgy growth and lipid composition. Two triplicate groups were established to test two experimental diets: (1) Control group fed a diet with no added carotenoids, and (2) canthaxanthin group (CTX100) fed a diet with 100 mg of synthetic can-thaxanthin per kilogram of diet (CTX). Final and eviscerated weight were increased (P < 0.05) in the CTX100 treatment. The rest of growth performance parameters were not affected by the CTX diet. Whole-fish total lipid content was decreased (P < 0.05) in CTX100 fish. In the liver, total lipids were not affected; however, saturated fatty acids in CTX100 treatment were significantly lower together with a higher n-3 PUFA and a lower n-6 PUFA, therefore increasing the n-3/n-6 ratio. Liver histology of CTX100 fish revealed decreased lipid vacuolization thus, significantly lowering hepato-cyte area. In the muscle, total lipids were not affected. Similar to the liver, an increase of n-3 PUFA and decrease n-6 PUFA, led to a significant increase of the n-3/n-6 ratio. Concerning plasma, only total cholesterol (TC) was significantly affected by the CTX diet. Dietary canthaxanthin has an effect on red porgy lipid composition.
... It has been widely used as a functional additive in aquaculture, mostly as exogenous pigment and antioxidant (Choubert, Cravedi, & Laurentie, 2009; Ingle de la Mora, Arredondo-Figueroa, Ponce-Palafox, Barriga-soca, & Vernon-Carter, 2006;Page & Davies, 2006;Ytrestoyl & Bjerkeng, 2007). The regulating effects of ASTX on lipid metabolism have been reported in terrestrial animals (Aoi et al., 2008;Bhuvaneswari, Arunkumar, Viswanathan, & Anuradha, 2010;Jia et al., 2012;Jia, Wu, Kim, Kim, & Lee, 2016;Kimura et al., 2014;McCarty, 2011), which suggested that ASTX has high potential to lower the lipid accumulation in plasma, liver and adipose tissue, although there were also contradictory results in some studies (Augusti et al., 2012;Kim et al., 2017;Ursoniu, Sahebkar, Serban, & Banach, 2015). ASTX has even been considered to be a candidate for preventing the development of nonalcoholic fatty liver disease (Yang et al., 2011(Yang et al., , 2014. ...
... Despite the relatively wide study on the lipid-regulating effects of ASTX in terrestrial animals such as mouse, rat and rabbit (Aoi et al., 2008;Augusti et al., 2012;Bhuvaneswari et al., 2010;Jia et al., 2012Jia et al., , 2016Kim et al., 2017;Kimura et al., 2014;McCarty, 2011;Ursoniu et al., 2015;Visioli & Artaria, 2017), relevant information in farmed fish was very limited even though ASTX has been used as pigment and antioxidant in fish feed. The present study provided new evidence for the lipid accumulation-regulating effects of ASTX in marine fish. ...
... context (Inoue et al., 2012). In the present study, however, the hepatic mRNA expression of PPARα1 and PPARβ was significantly low- In terrestrial animals, many studies indicated that ASTX exerts lipid-lowering effect via enhancing β-oxidation (Aoi et al., 2008;Kim et al., 2017). Besides the activation of PPARα in mice by ASTX, a study with apolipoprotein E knockout mice also showed that when fed a high-fat diet, mice fed ASTX (0.03% in the diet) for 4 weeks had increased gene expression of enzymes important for β-oxidation (e.g., CPT1 and acyl-CoA oxidase (ACOX)) (Yang et al., 2011), although there was also a study showing ASTX suppressed the actions of PPARα and the gene expression of its related molecules CPT1α and ACOX1 (Kobori et al., 2017). ...
Article
The lipid‐regulating effects of astaxanthin (ASTX) have been widely reported in terrestrial animals. However, little relevant information has been available in fish although ASTX has been used as exogenous pigment and antioxidant in fish feed. A 74‐day feeding study was conducted to investigate the effects of dietary ASTX on lipid accumulation in the marine teleost tiger puffer. Four experimental diets differing only in ASTX supplementation, that is, 0 (control), 50 (ASTX50), 100 (ASTX100) and 500 (ASTX500) mg kg‐1, were randomly assigned to 12 tanks of juvenile tiger puffer. Compared to control, the liver lipid content in group ASTX50 was significantly higher, while those in groups ASTX100 and ASTX500 were lower. The muscle lipid contents in group ASTX500 were significantly higher compared to control. Group ASTX50 had the best growth performances, while diet ASTX500 seemed to have adverse effects. In the liver, compared to control, groups ASTX50 and ASTX100 showed significantly lower mRNA expressions of genes related to triglycerol synthesis and fatty acid synthesis, transport and uptake, but higher expressions of genes related to β‐oxidation and monoglycerol hydrolysis. In the muscle, compared to control, ASTX100 showed higher expressions of genes related to β‐oxidation. ASTX50 resulted in higher contents of saturated and monounsaturated fatty acids but lower contents of n‐3 polyunsaturated fatty acids in fish. In conclusion, astaxanthin in diets for tiger puffer differentially regulated the lipid accumulation in the liver and muscle, both in dose‐dependent manners. Excess dietary astaxanthin (500 mg/kg) had adverse effects on tiger puffer.
... Introduction I t has been shown that supplementation with several kinds of antioxidants contained in natural foods can improve energy metabolism during exercise in animals and humans. (1)(2)(3)(4) For example, supplementation with specific carotenoids, flavonoids, and glutathione activates aerobic metabolism associated with elevated mitochondrial function in skeletal muscle, a major metabolic organ. (1,(5)(6)(7)(8) Because energy consumed in skeletal muscle is mainly supplied by carbohydrates and lipids, the activation of aerobic metabolism accelerates conversion from pyruvate to acetyl-CoA in glycolysis and utilization of fatty acids. ...
... (1)(2)(3)(4) For example, supplementation with specific carotenoids, flavonoids, and glutathione activates aerobic metabolism associated with elevated mitochondrial function in skeletal muscle, a major metabolic organ. (1,(5)(6)(7)(8) Because energy consumed in skeletal muscle is mainly supplied by carbohydrates and lipids, the activation of aerobic metabolism accelerates conversion from pyruvate to acetyl-CoA in glycolysis and utilization of fatty acids. This can suppress glycogen depletion and lactic acid generation during exercise. ...
... We and other researchers have previously shown that astaxanthin stimulates lipid metabolism in skeletal muscle through mitochondrial activation. (1,28) The flavonoids catechin and quercetin widely exist in fruit and vegetables including onions, apples, and various kinds of teas, and can activate aerobic metabolism and accelerate mitochondrial biogenesis. (2,7,8,28) In addition, it has recently been shown that glutathione, a factor contained in natural foods including fruit and vegetables, accelerates aerobic metabolism via mitochondrial biogenesis in skeletal muscle. ...
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Although supplementation with several antioxidants has been suggested to improve aerobic metabolism during exercise, whether dietary foods containing such antioxidants can exert the metabolic modulation is unclear. This study aimed to investigate the effect of intake of the specific antioxidant-rich foods coupled with exercise training on energy metabolism. Twenty young healthy, untrained men were assigned to antioxidant and control groups: participants in the antioxidant group were encouraged to consume foods containing catechin, astaxanthin, quercetin, glutathione, and anthocyanin. All participants performed cycle training at 60% maximum oxygen consumption for 30 min, 3 days per week for 4 weeks. Maximum work load was significantly increased by training in both groups, while oxygen consumption during exercise was significantly increased in the antioxidant group only. There were positive correlations between maximum work load and fat/carbohydrate oxidations in the antioxidant group. Carbohydrate oxidation during rest was significantly higher in the post-training than that in the pre-training only in the antioxidant group. More decreased levels of serum insulin and HOMA-IR after training were observed in the antioxidant group than in the control group. This study suggests that specific antioxidant-rich foods could modulate training-induced aerobic metabolism of carbohydrate and fat during rest and exercise.
... The antioxidative properties of ASTA have also been shown to protect enzymes, such as carnitine palmitoyltransferase 1 (CPT1) and adenosine monophosphate activated protein kinase from oxidative damage (Aoi et al., 2008(Aoi et al., , 2014. This can result in improvements to fat oxidation during exercise and improved endurance exercise performance in rodent models using ∼3to 5-week supplementation periods (Aoi et al., 2008(Aoi et al., , 2018Ikeuchi et al., 2006). ...
... The antioxidative properties of ASTA have also been shown to protect enzymes, such as carnitine palmitoyltransferase 1 (CPT1) and adenosine monophosphate activated protein kinase from oxidative damage (Aoi et al., 2008(Aoi et al., , 2014. This can result in improvements to fat oxidation during exercise and improved endurance exercise performance in rodent models using ∼3to 5-week supplementation periods (Aoi et al., 2008(Aoi et al., , 2018Ikeuchi et al., 2006). Furthermore, the antioxidative properties of ASTA have been used to facilitate recovery from strenuous exercise (Sztretye et al., 2019). ...
... Improvements in fat oxidation may also result in improvements to aspects of cardiometabolic health, especially since individuals with metabolic syndrome lack the ability to oxidize fats during exercise compared with more active counterparts (San-Millán & Brooks, 2018). With respect to substrate utilization during exercise, the antioxidative properties of ASTA have been suggested to support fat metabolism by reducing oxidation of CPT1 (Aoi et al., 2008). The CPT1 is an enzyme that facilitates the attachment and transport of long-chain fatty acids into the mitochondria via the carnitine transport mechanism. ...
Article
This study investigated the effects of 6 mg/day of astaxanthin supplementation on markers of oxidative stress and substrate metabolism during a graded exercise test in active young men. A double-blind, randomized, counterbalanced, cross-over design was used. Fourteen men (age = 23 ± 2 years) supplemented with 6 mg/day of astaxanthin and a placebo for 4 weeks, with a 1 week washout period between treatments. Following each supplementation period, a fasting blood sample was obtained to measure markers of oxidative stress: glutathione, hydrogen peroxide, advanced oxidation protein products, and malondialdehyde. Participants also completed a graded exercise test after each treatment to determine substrate utilization during exercise at increasing levels of intensity. Glutathione was ∼7% higher following astaxanthin compared with placebo (1,233 ± 133 vs. 1,156 ± 185 μM, respectively; p = .02, d = 0.48). Plasma hydrogen peroxide and malondialdehyde were not different between treatments ( p > .05). Although not statistically significant ( p = .45), advanced oxidation protein products were reduced by ∼28%. During the graded exercise test, mean fat oxidation rates were not different between treatments ( p > .05); however, fat oxidation decreased from 50 to 120 W ( p < .001) and from 85 to 120 W ( p = .004) in both conditions. Astaxanthin supplementation of 6 mg/day for 4 weeks increased whole blood levels of the antioxidant glutathione in active young men but did not affect oxidative stress markers or substrate utilization during exercise. Astaxanthin appears to be an effective agent to increase endogenous antioxidant status.
... AX inhibited the damaging effects of mitochondrial overload, including resulting in reduced muscle damage in rodents after heavy exercise [31], as well as reduced oxidative modification of skeletal muscle proteins, and reduced inflammatory markers after treadmill exercise in mildly obese mice given a high-fat diet [77]. These results suggest that AX may protect mitochondria from oxidative damage caused by ROS production when mitochondria are overloaded under conditions of physiological stress. ...
... We, among others, have shown that AX improves glucose and lipid metabolism and muscle strength [77,84,[89][90][91][92], mainly by correcting abnormal gene expression or protein modification in the mitochondria, which is altered during oxidative injury [77,93]. These effects are mainly attributed to the antioxidant effects of AX. ...
... We, among others, have shown that AX improves glucose and lipid metabolism and muscle strength [77,84,[89][90][91][92], mainly by correcting abnormal gene expression or protein modification in the mitochondria, which is altered during oxidative injury [77,93]. These effects are mainly attributed to the antioxidant effects of AX. ...
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Astaxanthin is a member of the carotenoid family that is found abundantly in marine organisms, and has been gaining attention in recent years due to its varied biological/physiological activities. It has been reported that astaxanthin functions both as a pigment, and as an antioxidant with superior free radical quenching capacity. We recently reported that astaxanthin modulated mitochondrial functions by a novel mechanism independent of its antioxidant function. In this paper, we review astaxanthin’s well-known antioxidant activity, and expand on astaxanthin’s lesser-known molecular targets, and its role in mitochondrial energy metabolism.
... However, mouse studies revealed that AST has the potential for promoting leanness. When mice are allowed to run on treadmills, presupplementation with AST enhances their endurance and promotes a more selective utilization of fat for fuel [51,52]. The increase in endurance presumably reflects, in part, a sparing of glycogen stores, so that it takes longer for running mice "to hit the wall" when glycogen is depleted. ...
... In one AST-mouse study, researchers found that the enzyme that is rate-limiting for fatty acid uptake into mitochondria was oxidatively modified in exercised mice. However, the long-term administration of AST alleviated the extent of this oxidative damage [52]. ...
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Phycocyanin (PhyCB), derived from specific microalgae, has demonstrated a potential to inhibit or diminish the adverse effects of oxidative stress and NOX in mice models. Treg induction and astaxanthin (AST) are vital factors to consider in further evaluating the bioactive and relevant pathways of discouraging disease and encouraging health. Treg cells play a vital role in inhibiting and regulating autoimmune disorders. PhyCB may replicate the Treg inductive activity of the biliverdin-bilirubin pathway. AST is a natural antioxidant that may be beneficial to mitochondrial membranes and other cellular membranes; thus, opposing oxidative stress to the mitochondria and the adverse productive of NOX. AST has been shown to protect mitochondria from oxidative damage in several cell culture studies. AST has been shown to promote a more selective utilization of fat during exercise, which, with PhyCB, should prove useful for endurance athletes, or for those who want to use exercise training to lose weight and maintain proper weight. Also, AST can have a favorable impact on metabolic syndrome. The concurrent administration or supplementation of PhyCB and AST shows promise in treating or preventing a wide array of human disorders.
... 8-10 indeed, aoi et al. reported that changes in redox homeostasis (i.e., increase in reactive species) can be associated with accelerated muscle glycogen utilization and decreased endurance performance in mice. 10 These findings suggest that changes in redox homeostasis may partly contribute to energy metabolism and lower performance levels during acute exercise. accordingly, various studies have been conducted to investigated the effects of exogenous antioxidants (e.g., vitamin c, vitamin e, and polyphenol) on redox biomarkers, energy metabolism, and performance level during acute exercise. ...
... accordingly, various studies have been conducted to investigated the effects of exogenous antioxidants (e.g., vitamin c, vitamin e, and polyphenol) on redox biomarkers, energy metabolism, and performance level during acute exercise. 5,[10][11][12] in recent years, h 2 has attracted widespread interest as a therapeutic agent. a study has reported that inhalation of h 2 gas (1 4%) could markedly suppress brain injury by buffering the effects of oxidative damage. ...
... However, mouse studies revealed that AST has the potential for promoting leanness. When mice are allowed to run on treadmills, presupplementation with AST enhances their endurance and promotes a more selective utilization of fat for fuel [51,52]. The increase in endurance presumably reflects, in part, a sparing of glycogen stores, so that it takes longer for running mice "to hit the wall" when glycogen is depleted. ...
... It could be interpreted that the oxidative stress generated in muscle by prolonged exercise might selectively damage the capacity of mitochondria to utilize fat for fuel. In one of the AST-mouse studies, the researchers found that the enzyme which is rate-limiting for fatty acid uptake into mitochondria was oxidatively modified in exercised mice; but long-term administration of AST alleviated the extent of this oxidative damage [52]. Thus, the combination of PhyCB and AST may prove useful for endurance athletes (in whom fat is a major fuel) and in people who want to use exercise training to achieve weight control. ...
Article
Phycocyanin (PhyCB), derived from specific microalgae, has demonstrated a potential to inhibit or diminish the adverse effects of oxidative stress and NOX in mice models. Treg induction and astaxanthin (AST) are vital factors to consider in further evaluating the bioactive and relevant pathways of discouraging disease and encouraging health. Treg cells play a vital role in inhibiting and regulating autoimmune disorders. PhyCB may replicate the Treg inductive activity of the biliverdin-bilirubin pathway. AST is a natural antioxidant that may be beneficial to mitochondrial membranes and other cellular membranes; thus, opposing oxidative stress to the mitochondria and the adverse productive of NOX. AST has been shown to protect mitochondria from oxidative damage in several cell culture studies. AST has been shown to promote a more selective utilization of fat during exercise, which, with PhyCB, should prove useful for endurance athletes, or for those who want to use exercise training to lose weight and maintain proper weight. Also, AST can have a favorable impact on metabolic syndrome. The concurrent administration or supplementation of PhyCB and AST shows promise in treating or preventing a wide array of human disorders.
... One possible mechanism of antioxidant and anti-inflammatory activities for astaxanthin is that it can affect the fluidity and the permeability of membrane systems, and further inhibit the penetration of oxidative substances and the initiation of a lipid peroxidation process (Barros et al., 2001). Furthermore, the previous study indicated that dietary astaxanthin could modulate the biological functions related to the lipid peroxidation and oxidative stress (Aoi et al., 2008). On the contrary, crabs fed the FO diet had significantly higher MDA and LPO in hemolymph and hepatopancreas than those fed the KO diet. ...
... In the present study, crabs fed the KO diet had the highest expression of cpt1 and hsl among all treatments. One possible mechanism may be through the regulating effect of astaxanthin, which facilitated the interaction between CPT I and SRB2 (Aoi et al., 2008). CPT1 is a mitochondrial enzyme responsible for the formation of acyl carnitines by catalyzing the transfer of the acyl group of a long-chain fatty acyl-CoA from coenzyme A to l-carnitine, which is a rate-limiting step in the oxidation of fatty acids (McGarry and Brown, 1997). ...
Article
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An six-week feeding trial was conducted to evaluate the effects of dietary n-3 polyunsaturated fatty acid (n-3 PUFA) lipid sources on growth performance, antioxidant capacity, tissue fatty acid profiles, and expression levels of genes involved in lipid metabolism of juvenile green mud crab (Scylla paramamosain) (initial weight 45.3 ± 0.07 g). Three isonitrogenous and isoenergetic experimental diets were formulated to contain fish oil (FO), krill oil (KO) and linseed oil (LO), respectively. The results indicated that crabs fed the KO diet had significantly higher percent weight gain (PWG), specific growth rate (SGR) and feed efficiency (FE) than those fed the LO diet, while no statistic differences were observed between KO and FO diets. Dietary FO could significantly increase the concentrations of malondialdehyde (MDA) and lipid hydroperoxide (LPO) in hemolymph and hepatopancreas compared to dietary KO and LO, similar results were found in the levels of hepatopancreas 8-hydroxy-2-deoxyguanosine (8-OHDG). Crabs fed the KO diet could significantly increase the activities of total superoxide dismutase (T-SOD) and catalase (CAT) in comparison with FO and LO diets. Crabs fed with FO and KO had significantly higher contents of 20:5n-3 (EPA) and 22:6n-3 (DHA) in hepatopancreas and muscle than those fed with LO. While dietary LO could significantly promote the accumulation of C18:3n-3 (ALA) in hepatopancreas and muscle. The anabolic pathway relevant genes: fas and 6 pg d were up-regulated in KO diet. The catabolic pathway relevant genes, hsl, was up-regulated in FO and KO diets, cpt1, was up-regulated in KO diet. Moreover, crabs fed diet supplemented with KO could significantly increase the expression levels of srb2, srebp1 and hnf4α. These findings will provide the reference for the development of the diet for the growth stage of S. paramamosain, and could contribute to deepen the understanding of the physiological metabolism of dietary fatty acids for S. paramamosain.
... The anti-obesity mechanisms of astaxanthin may be complex. For example, astaxanthin decreased myeloperoxidase and nitric oxide synthases and made splenocytes less sensitive to lipopolysaccharide stimulation [20]; increased the usage of lipids during exercise [21]; and was a novel selective peroxisome proliferator-activated receptor gamma (PPAR-γ) modulator that acted as an antagonist or agonist to exert its ameliorative effects on obesity and insulin resistance [22]. Recently, increasing numbers of studies reported the effect of gut microbiota on obesity [23][24][25][26]. ...
Article
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Astaxanthin is an important antioxidant with many biological activities such as anti-tumor, anti-obesity, cardioprotective, and immuno-modulatory activities. Most of these biological activities are derived from (3S,3'S)-astaxanthin, while the activities of (3R,3'R)-astaxanthin are rarely reported. The purpose of this study was to investigate the effect of (3R,3'R)-astaxanthin on lipid metabolism and gut microbiota in mice fed with a high-fat diet. In this work, 40 male C57BL/6 mice were divided into 8 groups fed a high-fat diet supplemented or not with (3R,3'R)-astaxanthin or Xanthophyllomyces dendrorhous for 8 weeks. The weight gain, energy intake, fat index, plasma triacylglycerol and cholesterol, liver triacylglycerol and cholesterol, and gut microbiota were determined. The results showed that the addition of (3R,3'R)-astaxanthin/X. dendrorhous to the high-fat diet as a supplement prevented weight gain, reduced plasma and liver triacylglycerol, and decreased plasma and liver total cholesterol. The addition of (3R,3'R)-astaxanthin/X. dendrorhous also regulated the gut microbiota of the mice, which optimized the ratio of Bacteroides to Firmicutes and increased the content of Verrucomicrobia, especially Akkermansia. The changes in the gut microflora achieved a healthier structure, thus reducing the incidence of obesity. Thus (3R,3'R)-Astaxanthin has the function of regulating lipid metabolism and gut microbiota to prevent obesity caused by a high-fat diet. The production strain of (3R,3'R)-astaxanthin, X. dendrorhous, has the same function as astaxanthin in preventing obesity caused by a high-fat diet, which reflects its potential ability as a probiotic drug.
... Among the various radicals produced under oxidative conditions, carotenoids seem to react more efficiently with peroxyl radicals (Stahl and Sies 2003); this, together with (Sies and Stahl 1995). Furthermore, there are many evidences that suggest that carotenoids may not only protect lipids from reactive oxygen species (ROS), but also may influence lipid desaturation and elongation (Bell et al. 2000;Tsukui et al. 2008) as well as b-oxidation (Aoi et al. 2008;Ikeuchi et al. 2006Ikeuchi et al. , 2007Yazawa 2008). In the present trial, although lipid metabolism was not directly evaluated, total lipid and fatty acid composition of whole fish and several important metabolic tissues was analysed. ...
Article
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A 120-day feeding trial was conducted to assess the possible effect of including dietary astaxanthin (ASTX), for different lengths of time prior to harvest, on red porgy growth performance, lipid and fatty acid composition and post-mortem skin colour. Four treatment groups were established with fish of initial weight of approximately 220 g. Control group was fed on a control diet (with no astaxanthin included) for the entire experiment. ASTX60 group was fed for the first 60 days of the trial on the control diet and 60 days before harvest on a diet with 100 mg of unesterified astaxanthin per kg-1 of diet (ASTX diet). ASTX90 group was fed for the first 30 days of the trial on control diet and 90 days before harvest on ASTX diet. ASTX120 group was fed on ASTX diet during the complete experiment. Results showed an enhancement of certain growth parameters due to ASTX diet and feeding period. In addition, a lipid-lowering effect on whole fish and liver was observed with increased feeding time with ASTX diet, as well as a significant variation of liver and head kidney fatty acid profiles. Concerning skin colouration, only ASTX90 and ASTX120 treatment groups presented adequate hue values throughout the 7 days post-mortem, similar to those reported for wild red porgy. However, skin chroma was close to wild specimens in ASTX120 treatment fish only and up to day three post-mortem. Skin lightness (L*) was not affected by astaxanthin inclusion. Feeding red porgy for a period of 90-120 days before harvest on ASTX diet seems to affect red porgy growth performance, lipid content and fatty acid profile. However, to achieve an adequate skin colouration, throughout a post-mortem period of 7 days, ASTX diet should be given 120 days before harvest.
... Concerning hepatic glycogen, a glycogen-sparing effect of AX was found in mice under situations of prolonged exercise [45]. There is evidence that dietary AX promotes lipid metabolism in mice [46]. Thus, the effect of dietary AX on lipid metabolism in rainbow trout deserves further investigation. ...
Article
Full-text available
A 13-week feeding trial was carried out with juvenile rainbow trout to test two diets: a control diet without astaxanthin (AX) supplementation (CTRL diet), and a diet supplemented with 100 mg/kg of synthetic AX (ASTA diet). During the last week of the feeding trial, fish were exposed to episodic hyperoxia challenge for 8 consecutive hours per day. Episodic hyperoxia induced physiological stress responses characterized by a significant increase in plasma cortisol and hepatic glycogen and a decrease in plasma glucose levels. The decrease of plasma glucose and the increase of hepatic glycogen content due to episodic hyperoxia were emphasized with the ASTA diet. Hyperoxia led to an increase in thiobarbituric acid-reactive substances in the muscle, diminished by dietary AX supplementation in both liver and muscle. Muscle and liver AX were increased and decreased respectively after 7-day episodic hyperoxia, leading to an increase in flesh redness. This augment of muscle AX could not be attributed to AX mobilization, since plasma AX was not affected by hyperoxia. Moreover, hyperoxia decreased most of antioxidant enzyme activities in liver, whereas dietary AX supplementation specifically increased glutathione reductase activity. A higher mRNA level of hepatic glutathione reductase, thioredoxin reductase, and glutamate-cysteine ligase in trout fed the ASTA diet suggests the role of AX in glutathione and thioredoxin recycling and in de novo glutathione synthesis. Indeed, dietary AX supplementation improved the ratio between reduced and oxidized glutathione (GSH/GSSG) in liver. In addition, the ASTA diet up-regulated glucokinase and glucose-6-phosphate dehydrogenase mRNA level in the liver, signaling that dietary AX supplementation may also stimulate the oxidative phase of the pentose phosphate pathway that produces NADPH, which provides reducing power that counteracts oxidative stress. The present results provide a broader understanding of the mechanisms by which dietary AX is involved in the reduction of oxidative status.
... Strenuous exercise can cause skeletal muscle damage, therefore nutritional strategies to minimize the exercise-induced skeletal muscle injury have been received considerable attention in the past decade. Astaxanthin supplementation increases lipid utilization and reduces body fat accumulation during exercise through the activation of (PGC-1α) (Bloomer 2007;Liu et al. 2014) and carnitine palmitoyltransferase I (CPT I) in skeletal muscle (Aoi et al. 2008). Exercise is associated with the overproduction of free radicals and associated oxidative stress in muscles and plasma. ...
... While the importance of skeletal muscle glycogen for exercise in mice has not reached a conclusion yet [37,38], mice seem to increase reliance on it as the exercise intensity becomes higher as well as human. For example, previous study reported that running exercise with higher speed (30 m/min) compared to that in the present study induced about 40% of glycogen reduction in skeletal muscle [39]. Other mouse study showed that an incremental running test induced large skeletal muscle glycogen depletion at exhaustion while liver glycogen was not depleted [40]. ...
Article
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We investigated the effects of nutrient intake timing on glycogen accumulation and its related signals in skeletal muscle after an exercise that did not induce large glycogen depletion. Male ICR mice ran on a treadmill at 25 m/min for 60 min under a fed condition. Mice were orally administered a solution containing 1.2 mg/g carbohydrate and 0.4 mg/g protein or water either immediately (early nutrient, EN) or 180 min (late nutrient, LN) after the exercise. Tissues were harvested at 30 min after the oral administration. No significant difference in blood glucose or plasma insulin concentrations was found between the EN and LN groups. The plantaris muscle glycogen concentration was significantly (p < 0.05) higher in the EN group—but not in the LN group—compared to the respective time-matched control group. Akt Ser473 phosphorylation was significantly higher in the EN group than in the time-matched control group (p < 0.01), while LN had no effect. Positive main effects of time were found for the phosphorylations in Akt substrate of 160 kDa (AS160) Thr642 (p < 0.05), 5'-AMP-activated protein kinase (AMPK) Thr172 (p < 0.01), and acetyl-CoA carboxylase Ser79 (p < 0.01); however, no effect of nutrient intake was found for these. We showed that delayed nutrient intake could not increase muscle glycogen after endurance exercise which did not induce large glycogen depletion. The results also suggest that post-exercise muscle glycogen accumulation after nutrient intake might be partly influenced by Akt activation. Meanwhile, increased AS160 and AMPK activation by post-exercise fasting might not lead to glycogen accumulation.
... However, exercise experiments in humans were equivocal, showing improved endurance as time trial performance in competitive cyclists (Earnest et al., 2011), vs. no significant improvement in well-trained cyclists (Res et al., 2013) and soccer players (Djordjevic et al., 2012). During exercise, some evidence from animal experiments supports enhanced fat utilization over carbohydrates (Ikeuchi et al., 2006;Aoi et al., 2008), yet no supplementation effect in endurance exercise and recovery was established (Brown et al., 2018). ...
Article
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Objectives: To examine the supplementation effects of the xanthophyll carotenoid Astaxanthin on physical performance and exertional heat strain in humans. Design: A randomized double blind placebo controlled trial. Methods: Twenty two male participants (Age: 23.14 ± 3.5 y, height: 175 ± 6 cm, body mass: 69.6 ± 8.7 kg, % body fat: 16.8 ± 3.8) received placebo (PLA, n = 10) or Astaxanthin (ATX, n = 12) 12 mg/day Per os (P.O), for 30 days, and were tested pre and post-supplementation with a maximal oxygen uptake (VO2 Max) test and the heat tolerance test (HTT) (2 h walk at 40°C, 40% relative humidity (RH), 5 kph, 2% incline). NIH database registration no. NCT02088242. Gas exchange, Heart rate (HR), Relative perceived exertion (RPE), and blood lactate were measured during the VO2 Max test. Heart rate (HR), rectal (Trec), and skin (Tskin) temperatures, RPE, and sweat rate (SR) were monitored in the HTT. Serum heat shock protein 72 (HSP72), Creatine phospho-kinase (CPK), C-reactive protein (CRP), and lipid profile were measured before and after the test. Results: The rise in blood lactate caused by the VO2 Max test was significantly diminished in the ATX group (9.4 ± 3.1 and 13.0 ± 3.1 mmole*l−1 in the ATX and PLA groups, respectively P < 0.02), as was the change in oxygen uptake during recovery (−2.02 ± 0.64 and 0.83 ± 0.79% of VO2 Max in the ATX and PLA group, respectively, p = 0.001). No significant differences were observed in the anaerobic threshold or VO2 Max. In the HTT, no significant physiological or biochemical differences were observed (HR <120 bpm, Trec rose by ~1°C to <38°C, no difference in SR). Conclusions: Astaxanthin supplementation improved exercise recovery. No benefit was observed for ATX over PLA in response to heat stress. Further examination of Astaxanthin in higher exertional heat strain is required.
... Several studies reported that mice fed daily with astaxanthin (0.02% w/w) for 4 weeks were able to significantly enhance the time to running exhaustion. 36 Double-blind parallel studies indicated that supplementation with astaxanthin (4 mg d −1 ) for 4 weeks significantly improved 20 km cycling trial performance of amateur trained male cyclists. 37 In contrast, an ergogenic benefit was not observed during a cycling exhaustion test in well-trained male cyclists or triathletes following a 4 weeks supplementation with 20 mg astaxanthin per day. ...
Article
The beneficial effects of nonpolar DHA/EPA in triacylglycerol (TG) and ethyl ester (EE) forms as well as terrestrial phospholipids on physical fatigue have been widely reported. However, the results involving the effects were inconsistent, and the reason might be that it usually ignored the differences between physical fatigue induced by aerobic and anaerobic exercise. Additionally, it has been reported the significant improvement of DHA/EPA esterified to phospholipids (DHA/EPA-PLs) on many fields but not physical fatigue. Therefore, the effects of DHA/EPA-PLs on physical fatigue induced by aerobic and anaerobic exercise were evaluated and compared with L-carnitine and astaxanthin using swimming and running exhaustion test in mice, respectively. The results showed that DHA/EPA-PL and L-carnitine had significant effects on the performance of aerobic exercise, while astaxanthin had remarkable effect on the performance of anaerobic exercise. The possible underlying mechanisms indicated that DHA/EPA-PL significantly promoted the carbohydrate and lipid metabolism as well as mitochondrial respiratory chain and tricarboxylic acid cycle in muscle. The study represented a potential novel candidate or targeted dietary patterns for alleviating physical fatigue.
... Another relevant property of astaxanthin is to affect the fluidity and the permeability of membrane systems (e.g., cytomembrane and mitochondrial membrane), which can inhibit the penetration of oxidative substances and the initiation of a lipid peroxidation process (Barros et al., 2001). The biological functions related to the lipid peroxidation and oxidative stress have been proved to be modulated by the astaxanthin levels in the diet (Aoi et al., 2008;Chien et al., 2003;Tejera et al., 2007). From the above, the diet supplemented with krill oil increases the dietary astaxanthin levels and reduces negative effects of high levels of n-3 PUFA (especially EPA and DHA) and enhances the capacity against lipid peroxidation and oxidative stress. ...
Article
The effects of dietary lipid sources on growth performance, feed utilization, hematological characteristics, antioxidant capacity and tissue fatty acid profiles were assessed in juvenile swimming crab (Portunus trituberculatus). Six isonitrogenous (approximately 45% crude protein)and isolipidic (approximately 8% crude lipid)experimental diets were formulated to contain fish oil (FO), krill oil (KO), palm oil (PO), rapeseed oil (RO), soybean oil (SO)and linseed oil (LO), respectively. 270 swimming crab juveniles (approximately initial weight 5.43 ± 0.03 g)were randomly stocked and sorted into 270 individual rectangle plastic baskets in three cement pools. The results showed that crabs fed the diet containing KO had a significantly higher percent weight gain (PWG), specific growth rate (SGR)and molting ratio (MR)than those fed the other diets. Crabs fed the KO diet had the lowest feed conversion ratio (FCR)among all treatments, followed by the FO diet. However, survival, daily feed intake (DFI)and hepatosomatic index (HSI)were not affected by the dietary lipid sources. Crabs fed the FO and KO diets led to significantly higher glucose (GLU)concentration in hemolymph compared to that fed the vegetable oils (VOs)diets. Moreover, a significant elevation of total protein (TP), glucose (GLU)and low density lipoprotein (LDL)was observed in hemolymph of crabs fed the KO diet. The activities of total superoxide dismutase (T-SOD)and total antioxidant capacity (T-AOC)as well as the content of glutathione (GSH)in hepatopancreas of crabs fed the KO diet had the highest value among all treatments. The minimum concentrations of MDA in hemolymph and hepatopancreas were observed in crabs fed the KO diet. The fatty acid compositions of tissues reflected that of diets and lipid sources. Crabs fed the FO and KO diets had significantly higher values of EPA, DHA and n-3/n-6 ratio in hepatopancreas and muscle than those fed the VOs diets. In summary, based on the growth response and antioxidant capacity in comparison to VOs even FO, KO appeared to be more effective and beneficial for juvenile swimming crab. This will provide reference for the development of the diet for the reproductive and developmental stage of swimming crab.
... Novelli et al., reported in 1990 that administering vitamin E intramuscularly substantially improved swimming performance in mice [128]. Similarly, numerous other studies have demonstrated that taking antioxidants improves endurance performance [129][130][131]. ...
Article
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It is well established that the increase in reactive oxygen species (ROS) and free radicals production during exercise has both positive and negative physiological effects. Among them, the present review focuses on oxidative stress caused by acute exercise, mainly on evidence in healthy individuals. This review also summarizes findings on the determinants of exercise-induced oxidative stress and sources of free radical production. Moreover, we outline the effects of antioxidant supplementation on exercise-induced oxidative stress, which have been studied extensively. Finally, the following review briefly summarizes future tasks in the field of redox biology of exercise. In principle, this review covers findings for the whole body, and describes human trials and animal experiments separately.
... It may also forestall obesity related metabolic disturbances and inflammation [126]. Aoi et al., found that AST increased the usage of lipids during exercise, culminating in a modified muscular metabolism, superior physical function, decreased body fat and enhanced improving muscular action during exercise [6,[127][128][129]. AST is a novel selective peroxisome proliferator-activated receptor gamma (PPAR-γ) modulator that acts as an antagonist or agonist to exert its ameliorative effects on obesity and insulin resistance [130]. ...
Article
Astaxanthin (AST) is a potent lipid-soluble keto-carotenoid with auspicious effects on human health. It protects organisms against a wide range of diseases with excellent safety and tolerability. Various imperative biological activities in vitro and in vivo models have been suggested for AST. This review article is focused on the therapeutic potentials, biological activities and benefical health effects of AST. The pharmacological mechanisms of action of AST in the treatment and prevention of the peripheral and central nervous system diseases was also reviewed to provide new insights to researchers. Finally, we suggested a novel hypothesis for the mechanism of action of AST in neuropathic pain following spinal cord injury.
... Concerning hepatic glycogen, a glycogen-sparing effect of AX was found in mice under situations of prolonged exercise [45]. There is evidence that dietary AX promotes lipid metabolism in mice [46]. Thus, the effect of dietary AX on lipid metabolism in rainbow trout deserves further investigation. ...
Article
Full-text available
A 13-week feeding trial was carried out with juvenile rainbow trout to test two diets: a control diet without astaxanthin (AX) supplementation (CTRL diet), and a diet supplemented with 100 mg/kg of synthetic AX (ASTA diet). During the last week of the feeding trial, fish were exposed to episodic hyperoxia challenge for 8 consecutive hours per day. Episodic hyperoxia induced physiological stress responses characterized by a significant increase in plasma cortisol and hepatic glycogen and a decrease in plasma glucose levels. The decrease of plasma glucose and the increase of hepatic glycogen content due to episodic hyperoxia were emphasized with the ASTA diet. Hyperoxia led to an increase in thiobarbituric acid-reactive substances in the muscle, diminished by dietary AX supplementation in both liver and muscle. Muscle and liver AX were increased and decreased respectively after 7-day episodic hyperoxia, leading to an increase in flesh redness. This augment of muscle AX could not be attributed to AX mobilization, since plasma AX was not affected by hyperoxia. Moreover, hyperoxia decreased most of antioxidant enzyme activities in liver, whereas dietary AX supplementation specifically increased glutathione reductase activity. A higher mRNA level of hepatic glutathione reductase, thioredoxin reductase, and glutamate-cysteine ligase in trout fed the ASTA diet suggests the role of AX in glutathione and thioredoxin recycling and in de novo glutathione synthesis. Indeed, dietary AX supplementation improved the ratio between reduced and oxidized glutathione (GSH/GSSG) in liver. In addition, the ASTA diet up-regulated glucokinase and glucose-6-phosphate dehydrogenase mRNA level in the liver, signaling that dietary AX supplementation may also stimulate the oxidative phase of the pentose phosphate pathway that produces NADPH, which provides reducing power that counteracts oxidative stress. The present results provide a broader understanding of the mechanisms by which dietary AX is involved in the reduction of oxidative status.
... Interestingly, β-carotene supplementation increases muscle mass and induces functional muscle hypertrophy in mice [219], via RAR [220]. Another carotenoid, astaxanthin, promoted lipid over glucose utilization during exercise by preventing the inhibitory oxidative modification of CPTI (the rate-limiting enzyme for fatty acid catabolism)which led to endurance improvement and a more efficient reduction of adipose tissue mass with training [221,222]. Astaxanthin supplementation also enhances the skeletal muscle's capacity for mitochondrial fatty acid oxidation in high-fat high-sucrose-fed obese mice, probably through PPARα transactivation, thereby preventing lipid accumulation in adipose tissue [223]. Overall, these reports illustrate that effects on skeletal muscle metabolism in basal and exercise conditions may contribute to the antiadiposity effects of retinoids and carotenoids. ...
Article
Antiobesity activities of carotenoids and carotenoid conversion products (CCPs) have been demonstrated in pre-clinical studies, and mechanisms behind have begun to be unveiled, thus suggesting these compounds may help obesity prevention and management. The antiobesity action of carotenoids and CCPs can be traced to effects in multiple tissues, notably the adipose tissues. Key aspects of the biology of adipose tissues appear to be affected by carotenoid and CCPs, including adipogenesis, metabolic capacities for energy storage, release and inefficient oxidation, secretory function, and modulation of oxidative stress and inflammatory pathways. Here, we review the connections of carotenoids and CCPs with adipose tissue biology and obesity as revealed by cell and animal intervention studies, studies addressing the role of endogenous retinoid metabolism, and human epidemiological and intervention studies. We also consider human genetic variability influencing carotenoid and vitamin A metabolism, particularly in adipose tissues, as a potentially relevant aspect towards personalization of dietary recommendations to prevent or manage obesity and optimize metabolic health. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.
... Redox imbalances during muscle activity can significantly contribute to the reduction of the contractile force, fatigability, and higher susceptibility to injuries. Therefore, it was proposed that dietary supplementation with antioxidants such as vitamin C, E, A, and lately carotenoids (the main precursors of fat soluble vitamin A) can decrease oxidative damage and improve performance as well as bypass muscle disorders [42,52,53]. Aoi and coworkers was first to demonstrate that AX is absorbed and transported into skeletal muscle and heart in mice [54]. ...
Article
Full-text available
Background: Astaxanthin (AX) a marine carotenoid is a powerful natural antioxidant which protects against oxidative stress and improves muscle performance. Retinol and its derivatives were described to affect lipid and energy metabolism. Up to date, the effects of AX and retinol on excitation-contraction coupling (ECC) in skeletal muscle are poorly described. Methods: 18 C57Bl6 mice were divided into two groups: Control and AX supplemented in rodent chow for 4 weeks (AstaReal A1010). In vivo and in vitro force and intracellular calcium homeostasis was studied. In some experiments acute treatment with retinol was employed. Results: The voltage activation of calcium transients (V50) were investigated in single flexor digitorum brevis isolated fibers under patch clamp and no significant changes were found following AX supplementation. Retinol shifted V50 towards more positive values and decreased the peak F/F0 of the calcium transients. The amplitude of tetani in the extensor digitorum longus was significantly higher in AX than in control group. Lastly, the mitochondrial calcium uptake was found to be less prominent in AX. Conclusion: AX supplementation increases in vitro tetanic force without affecting ECC and exerts a protecting effect on the mitochondria. Retinol treatment has an inhibitory effect on ECC in skeletal muscle.
... Antioxidants may prevent or delay various steps associated with carcinogenesis [36][37][38]. Carotenoid astaxanthin reduces oxidative stress, and inflammation [39,40] exerts a highly protective antioxidant effect [41]. Astaxanthin has been shown to decrease DNA damage and improve the immune response in healthy women after 8 weeks of intake [42]. ...
Article
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Ovarian clear cell carcinomas (OCCCs) are resistant to conventional anti-cancer drugs; moreover, the prognoses of advanced or recurrent patients are extremely poor. OCCCs often arise from endometriosis associated with strong oxidative stress. Of note, the stress involved in OCCCs can be divided into the following two categories: (a) carcinogenesis from endometriosis to OCCC and (b) factors related to treatment after carcinogenesis. Antioxidants can reduce the risk of OCCC formation by quenching reactive oxygen species (ROS); however, the oxidant stress-tolerant properties assist in the survival of OCCC cells when the malignant transformation has already occurred. Moreover, the acquisition of oxidative stress resistance is also involved in the cancer stemness of OCCC. This review summarizes the recent advances in the process and prevention of carcinogenesis, the characteristic nature of tumors, and the treatment of post-refractory OCCCs, which are highly linked to oxidative stress. Although therapeutic approaches should still be improved against OCCCs, multi-combinatorial treatments including nucleic acid-based drugs directed to the transcriptional profile of each OCCC are expected to improve the outcomes of patients.
... In the sports sector, astaxanthin was found to be of benefit for weight trained individuals with a high percentage area for fiber types IIA and IIAB/B due to being able to reduce the sensations of delayed-onset muscular soreness in muscle damage caused by exercise (Fry et al. 2004). Aoi et al. (2008), were able to show that astaxanthin helped during training by switching to lipid metabolism rather than glucose utilization; this is done through palmitoyltransferase I activation, leading to the improvement in endurance and a significant reduction in adipose tissue during exercise. The ability of astaxanthin to reduce glucose utilization was also studied by Ikeuchi et al. (2006) who also showed that it is able to increase fatty acid utilization to serve as an energy source during exercise. ...
Chapter
In this chapter, we are putting our focus on biologically active compounds that are taken from natural resources, specifically compounds that act on molecular targets and are involved in several diseases in the human body. One of the most well-known biologically active compounds is astaxanthin, which is a xanthophyll carotenoid found in Haematococcus pluvialis, Chlorella zofingiensis, Chlorococcum and Phaffia rhodozyma. Astaxanthin has shown to provide a wide range of beneficial health benefits on the metabolism and in several organ systems of the human body including cardiovascular diseases, neurological disorders, endocrine diseases, ophthalmic diseases, rheumatological diseases, dermatological diseases, immunological diseases, nephrological disorders and obstetrics and gynaecological conditions, including pre-eclampsia and fertility. Additionally, astaxanthin has shown to provide a comprehensive set of activities which are beneficial to the human body such as anti-cancer activity, anti-inflammatory activity, anti-apoptotic activity, anti-oxidant activity and anti-cancer activity. Moreover, astaxanthin is found to be effective in enhancing sports performance during physical activity and therapeutic for the smoking population due to the high anti-oxidant activity found in astaxanthin.
... [3] Still, it can act against many conditions like hypertension, diabetes, and obesity [4] by improving physical performance and reducing body fat. [5] Moreover, eye, brain, and skin health can also benefit from this compound. [6,7] Mostly, industrial-scale production of astaxanthin occurs by chemical methods, which are synthetized from petrochemicals and their derivatives. ...
Article
Astaxanthin is a xanthophyll carotenoid widely used in aquaculture and nutraceutical industries. Among natural sources, the microalga Haematococcus pluvialis is the non-genetically modified organism with the greatest capacity to accumulate astaxanthin. Therefore, it is important to understand emerging strategies in upstream and downstream processing of astaxanthin from this microalga. This review covers all aspects regarding the production and the market of natural astaxanthin from H. pluvialis. Astaxanthin biosynthesis, metabolic pathways, and nutritional metabolisms from green vegetative motile to red haematocyst stage were reviewed in detail. Also, traditional and emerging techniques on biomass harvesting and astaxanthin recovery were presented and evaluated. Moreover, the global market of astaxanthin was discussed, and guidelines for sustainability increasing of the production chain of astaxanthin from H. pluvialis were highlighted, based on biorefinery models. This review can serve as a baseline on the current knowledge of H. pluvialis and encourage new researchers to enter this field of research.
... Aoi found that ASTA facilitates the mutual promotion of CPT I and FAT/CD36 in exercise muscles. Changes in CPT I activity can affect the co-localization of CPT I with FAT/CD36, which regulates changes in lipid metabolism during exercise [30]. Moreover, Ikeuchi et al. found that the dietary supplementation of ASTA inhibited CPT I activity and promoted lipid metabolism in exercised rats as compared to mice with a normal diet [31]. ...
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Purpose: In this study, proton nuclear magnetic resonance (1H NMR) spectroscopy was used to evaluate the effect of astaxanthin (ASTA) supplementation on changes in human plasma elicited by high-intensity exercise. Methods: Sixteen adult males were randomly divided into 2 groups (n = 8 per group), namely the control group C (placebo for 28 d, 4 weeks) and experimental group M (supplement medium dose ASTA: 12 mg/d for 28 d, 4 weeks). At 08:00 on the 29th day, fasting blood sampling was carried out on all the participants, and the samples were tested in the laboratory for the first time. Later, the participants performed acute exercise on a pedal-powered bicycle with full strength for 30 s × 3/3 min intervals (loading a weight of 0.075 kg/kg). Blood sampling was then respectively performed immediately, 1 h after the acute exercise, and 1 d after the acute exercise. Results: (1) The metabolites of the subjects of the two groups were found to be diverse at different time points, and 34 types of metabolites were screened from the two groups. (2) The metabolites with differences between the two groups 1 h after exercise were β-hydroxybutyrate, creatine, and glycerol. The levels of β-hydroxybutyric acid and glycerol in group M were significantly lower than those in group C, while the level of creatine was significantly higher. Compared with the resting state 1 h after exercise, the metabolites in common between the two groups were leucine (Leu), valine (Val), and citric acid (CA), and their levels were significantly decreased. (3) During the period between 1 h and 1 d after exercise, the different metabolites between the two groups were methionine (Met) and glycerol. The glycerol levels of group M were significantly lower than those of group C, while the levels of Met were significantly higher. The co-metabolites of the subjects in groups C and M 1 d after exercise were creatine, glucose, and glycerol, the levels of which were all significantly increased. Conclusions: (1) One hour after exercise, the consumption of creatine, amino acids, fatty acids, and CA was found to be obvious, and ASTA intake was conducive to their recovery. (2) After high-intensity exercise, changes occurred in the body’s energy metabolism that involved the metabolism of glucose, lipids, and proteins, and basic recovery was found 1 d after exercise. The findings of this study suggest that ASTA intake can accelerate metabolic recovery induced by physical exercise.
... Salmon can experience burst swimming during farming operations such as moving between pens or delousing, or in the wild during up-river migration to spawn. Astaxanthin prevents oxidative damage in mitochondria (Wolff et al., 2010) and increases endurance and muscle performance in mammals (Ikeuchi et al., 2006;Aoi et al., 2008;Liu et al., 2014). Thus, it would be of interest to study the function and the fate of astaxanthin in salmon muscle during and after an exhaustive exercise. ...
Article
High content of carotenoids in tissues of salmonid species suggests possible functional importance, which has so far remained unclear. The objective of this study was to investigate the effect of astaxanthin on performance and gene expression of sea water adapted Atlantic salmon (Salmo salar) fed diets with low content of marine ingredients (7.5% fishmeal and 5% fish oil). Salmon with start weight 197 g were fed two diets with identical proximate composition except for the content of astaxanthin (<1 and 48 mg/kg, respectively) for 84 days. Absence of dietary astaxanthin caused significant transcriptome changes revealed with DNA microarray. The growth rate was not optimal for the two diet groups but was not affected by dietary astaxanthin concentration. Accumulation of lipid in the intestine and liver was found in salmon fed both diets, indicating malabsorption of lipid. Salmon fed the diet without astaxanthin had larger livers and higher fat content in liver due to accumulation of triglycerides, but the difference in fat content was not significant. Transcriptome responses in different organs suggested that lack of dietary astaxanthin may have functional consequences in salmon fed low marine diets. In the intestine of astaxanthin deprived salmon, decreased expression was observed in a suite of immune genes including genes of innate antiviral immunity, transporters and enzymes of glycan metabolism. Transcriptome responses in liver suggested effect of absence of astaxanthin on lipid metabolism and especially on increased biosynthesis of terpenoids and steroids and only minor effects on immune genes. The greatest transcriptome changes were observed in skeletal muscle in the absence of astaxanthin, with an up-regulation of immune-related genes (119) and multiple genes with well-established association with stress. The condition resembled a mild inflammation of the muscle. Small or moderate scale of gene expression changes were in concordance with equal growth performance of fish fed both diets, however their character may indicate potential risk of absence of dietary carotenoids.
... ASX treatment lowered serum glucose concentration and raised HDL concentration compared to the OO group. The specific lipid lowering effect of ASX occurs by facilitating the use of lipids by muscle (Aoi et al. 2008). ASX administration reduced lipid oxidation significantly and increased SOD activity in the liver that was caused by excess fructose intake (Kang et al. 2001;Curek et al. 2010). ...
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The liver is the primary site for fructose metabolism; therefore, the liver is susceptible to fructose related metabolic disturbances including metabolic insulin dysfunction, dyslipidemia and inflammation. We investigated whether astaxanthin (ASX) can modify hepatic nuclear factor-kappa B (NF-κB)/sirtuin-1 (SIRT-1) expression to alter oxidative stress caused by ingestion of excess fructose in rats. The animals were divided randomly into two x two factorially arranged groups: two regimens were given either water (W) or 30% fructose in drinking water (F). These two groups were divided further into two subgroups each: two treatments, either orally with 0.2 ml olive oil (OO) or 1 mg ASX/kg/day in 0.2 ml olive oil (ASX). Fructose administration increased serum glucose, triglycerides and very low density lipoproteins, and decreased serum concentration of high density lipoproteins; fructose did not alter serum total cholesterol. Excess fructose decreased hepatic superoxide dismutase (SOD) and increased hepatic NF-κB and MDA levels. ASX treatment increased hepatic SIRT-1 and decreased hepatic NF-κB and malondialdehyde (MDA) levels. ASX treatment decreased hepatic NF-κB and increased SOD levels, but did not alter MDA level in rats fed high fructose. ASX administration ameliorated oxidative stress caused by excess fructose by increasing hepatic NF-κB and SIRT-1 expression.
... While evidence in rodent studies shows improved endurance performance after chronic ASX supplementation [375,377,379], a study in athletes [222] found no ergogenic effect after chronic supplementation. A study in rodents [380] reported enhanced fat oxidation rate and sparing of muscle glycogen during exercise, which is suggestive of a possible ergogenic mechanism of action of ASX. Beneficial effects on post-exercise muscle recovery are equivocal in the limited human studies published (Table 1). ...
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Antioxidant supplements are commonly consumed by endurance athletes to minimize exercise-induced oxidative stress, with the intention of enhancing recovery and improving performance. There are numerous commercially available nutritional supplements that are targeted to athletes and health enthusiasts that allegedly possess antioxidant properties. However, most of these compounds are poorly investigated with respect to their in vivo redox activity and efficacy in humans. Therefore, this review will firstly provide a background to endurance exercise-related redox signalling and the subsequent adaptations in skeletal muscle and vascular function. The review will then discuss commonly available compounds with purported antioxidant effects for use by athletes. N-acetyl cysteine may be of benefit over the days prior to an endurance event; while chronic intake of combined 1000 mg vitamin C + vitamin E is not recommended during periods of heavy training associated with adaptations in skeletal muscle. Melatonin, vitamin E and α-lipoic acid appear effective at decreasing markers of exercise-induced oxidative stress. However, evidence on their effects on endurance performance are either lacking or not supportive. Catechins, anthocyanins, coenzyme Q10 and vitamin C may improve vascular function, however, evidence is either limited to specific sub-populations and/or does not translate to improved performance. Finally, additional research should clarify the potential benefits of curcumin in improving muscle recovery post intensive exercise; and the potential hampering effects of astaxanthin, selenium and vitamin A on skeletal muscle adaptations to endurance training. Overall, we highlight the lack of supportive evidence for most antioxidant compounds to recommend to athletes.
... Astaxanthin is also used as a dietary additive in the USA, Japan, South Korea, and Sweden [4]. Like another carotenoid, astaxanthin manifests high protective antioxidant [5,6] and anticancer [7,8] properties which decrease oxidative stress and inflammation [9,10], reduces rethrombosis after thrombolysis [11] and is efficient in ischemia-reperfusion [12], arterial hypertension [13], and dyslipidemia [14]. ...
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Aim: We examined regulatory function of astaxanthin on mRNA expression of nuclear factor κB (NF-κB) p65, interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) in peripheral blood mononuclear cells in pre and postpartum Murrah buffaloes during summer (temperature-humidity index [THI]=86; relative humidity [RH]=24) and winter (THI=58.74; RH=73) seasons. Materials and Methods: A total of 32 Murrah buffaloes apparently healthy and in their one to four parity were selected from National Dairy Research Institute herd and equally distributed randomly into four groups (control and supplemented groups of buffaloes during summer and winter season, respectively). All groups were fed according to the nutrient requirement of buffaloes (ICAR, 2013). The treatment group was supplemented with astaxanthin at 0.25 mg/kg body weight/animal/day during the period 30 days before expected date of calving and up to 30 days postpartum. Results: There was downregulation of NF-κB p65 gene in all the groups. NF-κB p65 mRNA expression was lower (p
... The production of ROS, which are strong oxidants and induce oxidative stress in cells, is already known to increase under certain stressful conditions. The oxidative stress often leads to an increased risk of diseases [35,38,42,46,94,98,118,[121][122][123]125,[137][138][139][140][141][142]. Accordingly, insufficient ingestion of antioxidants, such as carotenoids and α-tocopherol, might increase an organism's susceptibility to oxidative stress-related diseases. ...
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Carotenoids, one of the most common types of natural pigments, can influence the colors of living organisms. More than 750 kinds of carotenoids have been identified. Generally, carotenoids occur in organisms at low levels. However, the total amount of carotenoids in nature has been estimated to be more than 100 million tons. There are two major types of carotenoids: carotene (solely hydrocarbons that contain no oxygen) and xanthophyll (contains oxygen). Carotenoids are lipid-soluble pigments with conjugated double bonds that exhibit robust antioxidant activity. Many carotenoids, particularly astaxanthin (ASX), are known to improve the antioxidative state and immune system, resulting in providing disease resistance, growth performance, survival, and improved egg quality in farmed fish without exhibiting any cytotoxicity or side effects. ASX cooperatively and synergistically interacts with other antioxidants such as α-tocopherol, ascorbic acid, and glutathione located in the lipophilic hydrophobic compartments of fish tissue. Moreover, ASX can modulate gene expression accompanying alterations in signal transduction by regulating reactive oxygen species (ROS) production. Hence, carotenoids could be used as chemotherapeutic supplements for farmed fish. Carotenoids are regarded as ecologically friendly functional feed additives in the aquaculture industry.
... [6][7][8] In fact, ROS-induced mitochondrial dysfunction has been suggested to cause an excessive accumulation of fat. 9 Thus, it has been suggested that exercise-induced oxidative stress inhibits lipid metabolism during exercise. 10 Recently, many studies have shown that molecular hydrogen (H 2 ) has beneficial biological effects that attenuate oxidative stress and/or intensify mitochondrial function. [11][12][13] Originally, Ohsawa et al. 14 reported that H 2 could protect cells and tissues against oxidative stress by selectively reducing ROS. ...
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Aerobic exercise is widely accepted as a beneficial option for reducing fat in humans. Recently, it has been suggested that molecular hydrogen (H2) augments mitochondrial oxidative phosphorylation. Therefore, the hypothesis that inhaling H2 could facilitate lipid metabolism during aerobic exercise was investigated in the current study by measuring the breath acetone levels, which could be used as non-invasive indicators of lipid metabolism. This study aimed to investigate the effect of inhaling H2 on breath acetone output during submaximal exercise using a randomized, single-blinded, placebo-controlled, and cross-over experimental design. After taking a 20-minute baseline measurement, breath acetone levels were measured in ten male subjects who performed a 60% peak oxygen uptake-intensity cycling exercise for 20 minutes while inhaling either 1% H2 or a control gas. In another experiment, six male subjects remained in a sitting position for 45 minutes while inhaling either 1% H2 or a control gas. H2 significantly augmented breath acetone and enhanced oxygen uptake during exercise (P < 0.01). However, it did not significantly change oxidative stress or antioxidant activity responses to exercise, nor did it significantly alter the breath acetone or oxygen uptake during prolonged resting states. These results suggest that inhaling H2 gas promotes an exercise-induced increase in hepatic lipid metabolism. The study was approved by the Ethical Committee of Chubu University, Japan (approved No. 260086-2) on March 29, 2018.
... The special chow was prepared with the addition of 4 g/kg of AstaReal A1010 (dissolved in 100% ethanol) to the standard rodent pellet (protein 20%, carbohydrates 70%, fats 4%, fibers 5%, vitamins, micro-and macronutrients) for a final concentration of 0.02% AX. This concentration was chosen according to the literature [13,15]. The mice had ad libitum access to water and food intake. ...
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Astaxanthin is a lipid-soluble carotenoid influencing lipid metabolism, body weight, and insulin sensitivity. We provide a systematic analysis of acute and chronic effects of astaxanthin on different organs. Changes by chronic astaxanthin feeding were analyzed on general metabolism, expression of regulatory proteins in the skeletal muscle, as well as changes of excitation and synaptic activity in the hypothalamic arcuate nucleus of mice. Acute responses were also tested on canine cardiac muscle and different neuronal populations of the hypothalamic arcuate nucleus in mice. Dietary astaxanthin significantly increased food intake. It also increased protein levels affecting glucose metabolism and fatty acid biosynthesis in skeletal muscle. Inhibitory inputs innervating neurons of the arcuate nucleus regulating metabolism and food intake were strengthened by both acute and chronic astaxanthin treatment. Astaxanthin moderately shortened cardiac action potentials, depressed their plateau potential, and reduced the maximal rate of depolarization. Based on its complex actions on metabolism and food intake, our data support the previous findings that astaxanthin is suitable for supplementing the diet of patients with disturbances in energy homeostasis.
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Background: The beneficial effect of exercise combined with licorice flavonoid oil supplementation on visceral fat was investigated. Methods: Male Sprague-Dawley rats were divided into 4 groups: control, exercise (Ex), control with licorice flavonoid oil supplementation (LFO), and exercise with licorice flavonoid oil supplementation (ExLFO) groups. The rats in the Ex and ExLFO groups ran on a treadmill (20 degree incline at 20 m/min for 30 min/day) 5 times a week for 7 weeks, and those in the LFO and ExLFO groups were orally administered with licorice flavonoid oil daily using a feeding needle. Results: Exercise or licorice flavonoid oil supplementation resulted in the reduction of the visceral fat mass and adipocyte size, respectively. In addition, exercise combined with licorice flavonoid oil supplementation more effectively decreased both of these measures. Exercise alone increased the β-hydroxyacyl-CoA dehydrogenase (β-HAD) and citrate synthase (CS) activities from the soleus and plantaris muscles, and licorice flavonoid oil supplementation alone increased the hepatic carnitine palmitoyl transferase-2 (CPT-2) activity. Furthermore, the combination of exercise and licorice flavonoid oil supplementation enhanced the both muscular β-HAD and CS activities, and hepatic CPT-2 activity. Conclusions: These results suggested that exercise combined with licorice flavonoid oil supplementation might be effective to decrease visceral adipose tissue via enhancing skeletomuscular and hepatic fatty acids oxidative capacity.
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During exercise, skeletal muscles release cytokines, peptides, and metabolites that exert autocrine, paracrine, or endocrine effects on glucose homeostasis. In this study, we investigated the effects of secreted protein acidic and rich in cysteine (SPARC), an exercise-responsive myokine, on glucose metabolism in human and mouse skeletal muscle. SPARC-knockout mice showed impaired systemic metabolism and reduced phosphorylation of AMPK and protein kinase B in skeletal muscle. Treatment of SPARC-knockout mice with recombinant SPARC improved glucose tolerance and concomitantly activated AMPK in skeletal muscle. These effects were dependent on AMPK-γ3 because SPARC treatment enhanced skeletal muscle glucose uptake in wild-type mice but not in AMPK-γ3-knockout mice. SPARC strongly interacted with the voltage-dependent calcium channel, and inhibition of calcium-dependent signaling prevented SPARC-induced AMPK phosphorylation in human and mouse myotubes. Finally, chronic SPARC treatment improved systemic glucose tolerance and AMPK signaling in skeletal muscle of high-fat diet-induced obese mice, highlighting the efficacy of SPARC treatment in the management of metabolic diseases. Thus, our findings suggest that SPARC treatment mimics the effects of exercise on glucose tolerance by enhancing AMPK-dependent glucose uptake in skeletal muscle.-Aoi, W., Hirano, N., Lassiter, D. G., Björnholm, M., Chibalin, A. V., Sakuma, K., Tanimura, Y., Mizushima, K., Takagi, T., Naito, Y., Zierath, J. R., Krook, A. Secreted protein acidic and rich in cysteine (SPARC) improves glucose tolerance via AMP-activated protein kinase activation.
Chapter
Astaxanthin is known as a “marine carotenoid” and occurs in a wide variety of living organisms such as salmon, shrimp, crab, and red snapper. Astaxanthin antioxidant activity has been reported to be more than 100 times greater than that of vitamin E against lipid peroxidation and approximately 550 times more potent than that of vitamin E for singlet oxygen quenching. Astaxanthin doesn’t exhibit any pro-oxidant nature and its main site of action is on/in the cell membrane. To date, extensive important benefits suggested for human health include anti-inflammation, immunomodulation, anti-stress, LDL cholesterol oxidation suppression, enhanced skin health, improved semen quality, attenuation of common fatigue including eye fatigue, increased sports performance and endurance, limiting exercised-induced muscle damage, and the suppression of the development of lifestyle-related diseases such as obesity, atherosclerosis, diabetes, hyperlipidemia, and hypertension. Recently, there has been an explosive increase worldwide in both the research and demand for natural astaxanthin mainly extracted from the microalgae, Haematococcus pluvialis, in human health applications. Japanese clinicians are especially using the natural astaxanthin as add-on supplementation for patients who are unsatisfied with conventional medications or cannot take other medications due to serious symptoms. For example, in heart failure or overactive bladder patients, astaxanthin treatment enhances patient’s daily activity levels and QOL. Other ongoing clinical trials and case studies are examining chronic diseases such as non-alcoholic steatohepatitis, diabetes, diabetic nephropathy, and CVD, as well as infertility, atopic dermatitis, androgenetic alopecia, ulcerative colitis, and sarcopenia. In the near future, astaxanthin may secure a firm and signature position as medical food.
Chapter
Satsuma mandarin (Citrus unshiu Marc.), a unique Japanese citrus species, is one of the foods which have most abundant β-cryptoxanthin all over the world. In this study, β-cryptoxanthin has a variety of health-promoting functions such as the body fat reducing, cosmetic (whitening), and osteoporosis prevention. β-Cryptoxanthin has also been shown in human studies to have anti-exercise fatigue and diabetes prevention actions. These multiple functions further support that β-cryptoxanthin may play a role in vitamin A function.
Chapter
Astaxanthin is a carotenoid that has potent protective effects on diabetic kidney disease (DKD) in diabetic mice models. DNA microarray study clearly demonstrated the involvement of mitochondrial oxidative phosphorylation pathway in the renal glomerular cells of diabetic mice and also showed that the expression of upregulated genes associated with this pathway was decreased by the treatment with astaxanthin. Proteomic analysis confirmed that the increases of 4-hydroxy-2-nonenal (HNE)- and Nε-(hexanonyl)lysine (HEL)-modified proteins were inhibited by the treatment with astaxanthin. These results demonstrated that astaxanthin exerts a protective effect against hyperglycemia-induced DKD by attenuating mitochondrial oxidative stress and subsequent cellular dysfunction.
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Background and aim Previous studies lack consistent conclusions as to whether astaxanthin is actually linked to various health benefits as claimed. Here, we attempt to unravel the association of astaxanthin consumption with selected health benefits by performing a systematic review and meta-analysis. Methods Online literature search databases including Scopus, Web of Science, PubMed/Medline, Embase and Google Scholar were searched to discover relevant articles available up to 17 March 2020. We used mean changes and SD of the outcomes to assess treatment response from baseline and mean difference, and 95 % CI were calculated to combined data and assessment effect sizes in astaxanthin and control groups. Results 14 eligible articles were included in the final quantitative analysis. Current study revealed that astaxanthin consumption was not associated with FBS, HbA1c, TC, LDL-C, TG, BMI, BW, DBP, and SBP. We did observe an overall increase in HDL-C (WMD: 1.473 mg/dl, 95 % CI: 0.319–2.627, p = 0.012). As for the levels of CRP, only when astaxanthin was administered (i) for relatively long periods (≥ 12 weeks) (WMD: -0.528 mg/l, 95 % CI: -0.990 to -0.066), and (ii) at high dose (> 12 mg/day) (WMD: -0.389 mg/dl, 95 % CI: -0.596 to -0.183), the levels of CRP would decrease. Conclusion In summary, our systematic review and meta-analysis revealed that astaxanthin consumption was associated with increase in HDL-C and decrease in CRP. Significant associations were not observed for other outcomes.
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This research was to determine effects of supplemental dietary microalgal astaxanthin (AST) on hepatic gene expression and protein production of redox enzymes, heat shock proteins (HSPs), cytokines, and lipid metabolism in broilers (BR) and laying hens (LH) under high ambient temperatures. A total of 240 (day old) Cornish male BR and 50 (19 wk old) White Leghorn Shavers LH were allotted in 5 dietary treatments with 6 and 10 cages/treatment (8 BR or 1 LH/cage), respectively. The birds were fed corn-soybean meal basal diets supplemented with microalgal (Haematococcus pluvialis) AST at 0, 10, 20, 40, and 80 mg/kg diet for 6 wk. Supplemental AST to the BR diet linearly decreased (P
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Objectives This study aimed to investigate whether supplementation with 12 mg⋅day⁻¹ astaxanthin for 7 days can improve exercise performance and metabolism during a 40 km cycling time trial. Design A randomised, double-blind, crossover design was employed. Methods Twelve recreationally trained male cyclists (VO2peak: 56.5 ± 5.5 mL⋅ kg⁻¹⋅ min⁻¹, Wmax: 346.8 ± 38.4 W) were recruited. Prior to each experimental trial, participants were supplemented with either 12 mg⋅day⁻¹ astaxanthin or an appearance-matched placebo for 7 days (separated by 14 days of washout). On day 7 of supplementation, participants completed a 40 km cycling time trial on a cycle ergometer, with indices of exercise metabolism measured throughout. Results Time to complete the 40 km cycling time trial was improved by 1.2 ± 1.7% following astaxanthin supplementation, from 70.76 ± 3.93 min in the placebo condition to 69.90 ± 3.78 min in the astaxanthin condition (mean improvement = 51 ± 71 s, p = 0.029, g = 0.21). Whole-body fat oxidation rates were also greater (+0.09 ± 0.13 g min⁻¹, p = 0.044, g = 0.52), and the respiratory exchange ratio lower (-0.03 ± 0.04, p = 0.024, g = 0.60) between 39–40 km in the astaxanthin condition. Conclusions Supplementation with 12 mg day⁻¹ astaxanthin for 7 days provided an ergogenic benefit to 40 km cycling time trial performance in recreationally trained male cyclists and enhanced whole-body fat oxidation rates in the final stages of this endurance-type performance event.
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Oxidative stress triggers the formation of lipid droplets in the liver by stimulating lipogenesis and simultaneously suppresses lipoprotein secretion under hypernutritional conditions. Herein we report on the observation of systemic organ failure that is associated with lipid droplet accumulation in fasting, SOD1-knockout (KO) mice. Upon a three-day fasting period, the KO mice were observed to be vulnerable, could not be rescued by refeeding and had largely died, while wild-type mice were totally recovered. Visceral fat was rapidly consumed during fasting, which resulted in energy shortage and increased fatality in the KO mice. Lipid droplets had accumulated and continued to remain in KO mouse organs that routinely catalyze fatty acids via β-oxidation, even though the levels of free fatty acids and β-hydroxybutyrate, a ketone body, in blood plasma were less in KO mice compared to WT mice during the fasting period. The fasting-triggered organ failure in the KO mice was effectively mitigated by feeding a high calorie-diet for 2 weeks prior to fasting, even though the mice had an excessive accumulation of lipid droplets in the liver. These collective data suggest that the lipid-catabolizing system is the sensitive target of oxidative stress triggered by fasting conditions in the KO mice.
Chapter
Among five subtypes of epithelial ovarian cancers, ovarian clear cell carcinomas (OCCCs) are the ones most strongly linked to oxidative stress. Oxidative stress is involved in the development of OCCCs, i.e., the malignant transformation of endometriosis to OCCC; therefore, oxidative stress should be considered as a therapeutic target for treating OCCC. Antioxidant intake is suggested as a mode of prevention, in addition to the removal of oxidative stress by surgery and hormonal therapy. Since OCCC develops under strong oxidative stress, it retains resistance to oxidative stress and therapy, leading to poor prognosis. Overexpression of hepatocyte nuclear factor 1 homeobox B and abundance of mitochondrial superoxide dismutase are related to the acquired resistance to oxidative stress in OCCCs. Studies on several therapeutic targets are in progress, which include receptor tyrosine kinase pathway molecules, antioxidative stress molecules, AT-rich interactive domain 1A-related chromatin remodeling factors, and genomic instability. This review outlines carcinogenesis, prevention, molecular biological characteristics, and potential therapeutics for treating OCCCs in the future.
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Astaxanthin, one of the dominant carotenoids in marine animals, showed both a strong quenching effect against singlet oxygen, and a strong scavenging effect against free radicals. These effects are considered to be defence mechanisms in the animals for attacking these active oxygen species. The activities of astaxanthin are approximately 10 times stronger than those of other carotenoids that were tested, namely zeaxanthin, lutein, tunaxanthin, canthaxanthin and β-carotene, and 100 times greater than those of a tocopherol. Astaxanthin also showed strong activity as an inhibitor of lipid peroxidation mediated by these active forms of oxygen. From these results, astaxanthin has the properties of a “SUPER VITAMIN E”.
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Background/aims: Carnitine is a co-factor of the enzymatic system involved in long chain fatty acid transport across the mitochondrial membrane. This physiological role of carnitine raised the hypothesis that this compound could act as a 'fat burner' by optimizing fat oxidation and consequently reducing its availability for storage. Our aim was to verify whether carnitine supplementation could maximize fat mass loss in trained rats. Methods: Male Wistar rats (200 g) were divided into four groups: control (C), sedentary supplemented (S), trained (T) and trained supplemented (TS). The training protocol consisted of bouts of swimming exercise (60 min x day(-1)) for 6 weeks. During the last 14 days, before sacrifice, the supplemented groups received a daily dose of 28 mg x kg(-1) of L-carnitine. Carcass fat content, weight and fat content of adipose tissues were evaluated in all experimental groups. Results: Our results indicate that carnitine feeding, per se, failed to promote fat mass loss. Endurance training successfully induced a decrease in the fat content in the carcass (28%) and the weight of adipose tissues (retroperitoneal and mesenteric depots by 41 and 20%, respectively) in comparison to C. Despite the augmented carnitine content in the soleus mitochondria (2-fold) observed in TS, the higher content did not maximize the fat loss induced by endurance training. Conclusions: Our data strongly suggest that endurance training, rather than carnitine content, is the major factor involved in fat mass loss.
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Mutations caused by oxidative DNA damage may contribute to human disease. A major product of that damage is 8-hydroxyguanine (oh8Gua). Because of differences in experimental design, the base pairing specificity of oh8G in vivo is not completely resolved. Here, oh8dGTP and DNA polymerase were used in two complementary bacteriophage plaque color assays to examine the mutagenic specificity of oh8Gua in vivo. The first is a reversion assay that detects all three single-base substitutions caused by misreading of guanine analogues inserted at a specific site. oh8Gua at that site gave a mutation frequency of 0.7%. Twenty-two of the 23 mutations were G----T substitutions. The second assay, a forward mutation assay, tests the mispairing potential of any altered nucleotide 1) during incorporation as substrate nucleotide, and 2) after multiple incorporations into a single-stranded DNA gap region of M13mp2. Substituting oh8dGTP for dGTP during polymerization produced 16% mutants; two classes of mutations were observed, both caused by pairing of oh8Gua with A. Seventy-six of 78 mutations were A----C substitutions, and two were G----T substitutions. These assays thus illustrate mutagenic replication of oh8Gua as template causing G----T substitutions and misincorporation of oh8Gua as substrate causing A----C substitutions, both caused by oh8Gua.A mispairs.
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The objectives of this study were to estimate the structure of the lipid hydroperoxide-modified lysine residue and to prove the presence of the adducts in vivo. The reaction of lipid hydroperoxide toward the lysine moiety was investigated employingN-benzoyl-glycyl-l-lysine (Bz-Gly-Lys) as a model compound of Lys residues in protein and 13-hydroperoxyoctadecadienoic acid (13-HPODE) as a model of the lipid hydroperoxides. One of the products, compound X, was isolated from the reaction mixture of 13-HPODE and Bz-Gly-Lys and was then identified as N-benzoyl-glycyl-N ε-(hexanonyl)lysine. To prove the formation of N ε-(hexanonyl)lysine, named HEL, in protein exposed to the lipid hydroperoxide, the antibody to the synthetic hexanonyl protein was prepared and then characterized in detail. Using the anti-HEL antibody, the presence of HEL in the lipid hydroperoxide-modified proteins and oxidized LDL was confirmed. Furthermore, the positive staining by anti-HEL antibody was observed in human atherosclerotic lesions using an immunohistochemical technique. The amide-type adduct may be a useful marker for the lipid hydroperoxide-derived modification of biomolecules.
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(-)-Hydroxycitrate (HCA) is an active ingredient that is extracted from the rind of the Indian fruit, Garcinia cambogia, which is available as an herbal supplement and is used to lose weight. In this study, the acute and chronic effects of HCA on energy metabolism were examined in male Std ddY mice. Mice were placed into metabolic chambers and administered 10 mg HCA or water (control) orally. Serum free fatty acid levels were significantly higher 100 min after administration in the HCA group, but the respiratory exchange ratio was not different from that in the control group. The concentration of glycogen in the gastrocnemius muscle was higher in the HCA group 16 h after administration, and in a separate study, the maximum swimming time until fatigue was slightly longer (P: = 0. 21) than that in the control group on d 1. The difference was significant on d 3 after 3 d of HCA or water administration. Other mice were administered 10 mg HCA or water orally twice a day for 25 d. On d 26, they were placed into metabolic chambers after administration and allowed to rest for 1 h, followed by 1 h of running at 15 m/min. Respiratory gas was monitored. The respiratory exchange ratio was significantly lower in the HCA group during both resting and exercising conditions. These results suggest that chronic administration of HCA promotes lipid oxidation and spares carbohydrate utilization in mice at rest and during running.
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Dietary antioxidants may attenuate oxidative damage from strenuous exercise in various tissues. Beneficial effects of the antioxidant astaxanthin have been demonstrated in vitro, but not yet in vivo. We investigated the effect of dietary supplementation with astaxanthin on oxidative damage induced by strenuous exercise in mouse gastrocnemius and heart. C57BL/6 mice (7 weeks old) were divided into groups: rested control, intense exercise, and exercise with astaxanthin supplementation. After 3 weeks of exercise acclimation, both exercise groups ran on a treadmill at 28 m/min until exhaustion. Exercise-increased 4-hydroxy-2-nonenal-modified protein and 8-hydroxy-2'-deoxyguanosine in gastrocnemius and heart were blunted in the astaxanthin group. Increases in plasma creatine kinase activity, and in myeloperoxidase activity in gastrocnemius and heart, also were lessened by astaxanthin. Astaxanthin showed accumulation in gastrocnemius and heart from the 3 week supplementation. Astaxanthin can attenuate exercise-induced damage in mouse skeletal muscle and heart, including an associated neutrophil infiltration that induces further damage.
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We have examined oxidized proteins in the brain regions of wild-type (WT) and ApoE-knockout (KO) animals. Total protein oxidation in the hippocampus of young-KO (6 month) animals was approximately 2-fold greater than that of young-WT (6 month) animals and was similar to that of old-WT (18 month) and old-KO (18 month) animals. In the cortex of the same animals, the levels of total protein oxidation in all four groups were not significantly different. Two-dimensional electrophoresis (2-DE) coupled with immunostaining for protein carbonylation revealed six specific oxidation-sensitive proteins, the oxidation levels of which were increased in young-KO, old-WT, and old-KO mice compared with young-WT mice. These six oxidation-sensitive proteins were identified by mass spectrometry as glial fibrillary acidic protein, creatine kinase BB, disulfide isomerase, chaperonin subunit 5, dihydropyrimidase-related protein 2, and mortalin. These results indicate that the ApoE gene product offers protection against age-associated oxidative damage in the brain. Moreover, two of these proteins, creatine kinase and dihydropyrimidase-related protein 2, have recently been found to be oxidized in the brains of human subjects with Alzheimer's disease [Aksenov et al. J. Neurochem. 74: 2520-2527; 2000; Castegna et al. J. Neurochem. 82: 1524-1532; 2002]. These data suggest that the ApoE-knockout mouse serves as an appropriate model for studying pathogenic oxidative mechanisms influencing risk and progression of Alzheimer's disease.
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First conceptualized as a mechanism for the mitochondrial transport of long-chain fatty acids in the early 1960s, the carnitine palmitoyltransferase (CPT) system has since come to be recognized as a pivotal component of fuel homeostasis. This is by virtue of the unique sensitivity of the outer membrane CPT I to the simple molecule, malonyl-CoA. In addition, both CPT I and the inner membrane enzyme, CPT II, have proved to be loci of inherited defects, some with disastrous consequences. Early efforts using classical approaches to characterize the CPT proteins in terms of structure/function/regulatory relationships gave rise to confusion and protracted debate. By contrast, recent application of molecular biological tools has brought major enlightenment at an exponential pace. Here we review some key developments of the last 20 years that have led to our current understanding of the physiology of the CPT system, the structure of the CPT isoforms, the chromosomal localization of their respective genes, and the identification of mutations in the human population.
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The dityrosine bond (DT) is an oxidative covalent cross-link between two tyrosines. DT cross-linking is increasingly identified as a marker of oxidative stress, aging and disease, and has been detected in diverse pathologies. While DT cross- linked proteins have been documented, the consequences of the DT link on the structure and function of the so modified proteins are yet to be understood. With this in view, we have studied the properties of intermolecular DT-dimers of four proteins of diverse functions, namely the enzyme ribonuclease A, the signal protein calmodulin, and the eye lens proteins alpha- and gamma B-crystallins. We find that DT is formed through radical reactions and type I photosensitization (including •OH, O2 •– and OONO–), but not by 1O2 and NO2 – (which modify his, trp and met more readily). Tyr residues on the surface of the protein make DT bonds (intra- and intermolecular) most readily and preferentially. The conformation of each of these DT-dimers, monitored by spectroscopy, is seen not to be significantly altered in comparison to that of the parent monomer, but the structural stability of the DT cross-linked molecule is lower than that of the parent native monomer. The DT-dimer is denatured at a lower temperature, and at lower concentrations of urea or guanidinium chloride. The effect of DT-cross-linking on the biological activities of these proteins was next studied. The enzymatic activity of the DT-dimer of ribonuclease A is not lost but lowered. DT-dimerization of lens alpha-crystallin did not significantly affect the chaperone-like ability; it inhibits the self-aggregation and precipitation of target proteins just as well as the parent, unmodified alpha-crystallin does. DT-dimerization of gamma B-crystallin is however seen to lead to more ready aggregation and precipitation, a point of interest in cataract. In the case of calmodulin, we could generate both intermolecular and intramolecular DT cross-linking, and study both the DT-dimer and DT-monomer. The DT-dimer binds smooth muscle light chain kinase and also Ca2+, but less efficiently and over a broad concentration range than the native monomer. The intramolecular DT-monomer is weaker in all these respects, presumably since it is structurally more constrained. These results suggest that DT cross-linking of globular proteins weakens their structural stability and compromises (though does not abolish) their biological activity, both of which are pathologically relevant. The intramolecular DT cross-link would appear to lead to more severe structural and functional consequences.
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Anthocyanins, which are used as a food coloring, are widely distributed in human diets, suggesting that we ingest large amounts of anthocyanins from plant-based foods. Mice were fed control, cyanidin 3-glucoside-rich purple corn color (PCC), high fat (HF) or HF + PCC diet for 12 wk. Dietary PCC significantly suppressed the HF diet-induced increase in body weight gain, and white and brown adipose tissue weights. Feeding the HF diet markedly induced hypertrophy of the adipocytes in the epididymal white adipose tissue compared with the control group. In contrast, the induction did not occur in the HF + PCC group. The HF diet induced hyperglycemia, hyperinsulinemia and hyperleptinemia. These perturbations were completely normalized in rats fed HF + PCC. An increase in the tumor necrosis factor (TNF)-alpha mRNA level occurred in the HF group and was normalized by dietary PCC. These results suggest that dietary PCC may ameliorate HF diet-induced insulin resistance in mice. PCC suppressed the mRNA levels of enzymes involved in fatty acid and triacylglycerol synthesis and lowered the sterol regulatory element binding protein-1 mRNA level in white adipose tissue. These down-regulations may contribute to triacylglycerol accumulation in white adipose tissue. Our findings provide a biochemical and nutritional basis for the use of PCC or anthocyanins as a functional food factor that may have benefits for the prevention of obesity and diabetes.
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We examined intra- and extracellular H(2)O(2) and NO formation during contractions in primary rat skeletal muscle cell culture. The fluorescent probes DCFH-DA/DCFH (2,7-dichlorofluorescein-diacetate/2,7-dichlorofluorescein) and DAF-2-DA/DAF-2 (4,5-diaminofluorescein-diacetate/4,5-diaminofluorescein) were used to detect H(2)O(2) and NO, respectively. Intense electrical stimulation of muscle cells increased the intra- and extracellular DCF fluorescence by 171% and 105%, respectively, compared with control nonstimulated cells (p <.05). The addition of glutathione (GSH) or Tiron prior to electrical stimulation inhibited the intracellular DCFH oxidation (p <.05), whereas the addition of GSH-PX + GSH inhibited the extracellular DCFH oxidation (p <.05). Intense electrical stimulation also increased (p <.05) the intra- and extracellular DAF-2 fluorescence signal by 56% and 20%, respectively. The addition of N(G)-nitro-L-arginine (L-NA) completely removed the intra- and extracellular DAF-2 fluorescent signal. Our results show that H(2)O(2) and NO are formed in skeletal muscle cells during contractions and suggest that a rapid release of H(2)O(2) and NO may constitute an important defense mechanism against the formation of intracellular (*)OH and (*)ONOO. Furthermore, our data show that DCFH and DAF-2 are suitable probes for the detection of ROS and NO both intra- and extracellularly in skeletal muscle cell cultures.
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1. The experiments were conducted to evaluate astaxanthin (Ax) uptake in several tissues and plasma lipoproteins of male broiler chickens fed on Phaffia rhodozyma containing a high concentration of Ax. 2. Male broiler chicks (5 weeks of age) fasted for 16h were given 0 or 45 mg Ax as Phaffia rhodozyma through the crop and blood was collected over the following 24 h. Ax appeared in the plasma at 2 h after administration into the crop. Most (more than 70%) of the Ax was contained in the high density lipoprotein (HDL) fraction in the plasma irrespective of blood sampling times and administration procedure of Ax. 3. Male broiler chicks (2 weeks of age) were fed on a diet containing 0, 50 or 100 mg/kg of yeast Ax for 2 weeks. Of the tissues examined, Ax concentration in the small intestine was highest, followed by subcutaneous fat, abdominal fat, spleen, liver, heart, kidney and skin. The lowest concentration was in the muscles. Ax concentration in the small intestine, subcutaneous fat, abdominal fat, liver and skin rose as dietary content increased, but this was not the case for the spleen, heart, kidney and muscles except for M. pecloralis superficialis. 4. Over 50% of Ax deposited in liver tissues was detected in the microsomal fraction and 15% was in the mitochondrial fraction. In muscles, both fractions of mitochondria and sarcoplasmic reticulum contained Ax.
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Fatty acid translocase (FAT)/CD36 is a long chain fatty acid transporter present at the plasma membrane, as well as in intracellular pools of skeletal muscle. In this study, we assessed the unexpected presence of FAT/CD36 in both subsarcolemmal and intermyofibril fractions of highly purified mitochondria. Functional assessments demonstrated that the mitochondria could bind (14)C-labeled palmitate, but could only oxidize it in the presence of carnitine. However, the addition of sulfo-N-succinimidyl oleate, a known inhibitor of FAT/CD36, resulted in an 87 and 85% reduction of palmitate oxidation in subsarcolemmal and intermyofibril fractions, respectively. Further studies revealed that maximal carnitine palmitoyltransferase I (CPTI) activity in vitro was inhibited by succinimidyl oleate (42 and 48% reduction). Interestingly, CPTI immunoprecipitated with FAT/CD36, indicating a physical pairing. Tissue differences in mitochondrial FAT/CD36 protein follow the same pattern as the capacity for fatty acid oxidation (heart > red muscle > white muscle). Additionally, chronic stimulation of hindlimb muscles (7 days) increased FAT/CD36 expression and also resulted in a concomitant increase in mitochondrial FAT/CD36 content (46 and 47% increase). Interestingly, with acute electrical stimulation of hindlimb muscles (30 min), FAT/CD36 expression was not altered, but there was an increase in the mitochondrial content of FAT/CD36 compared with the non-stimulated control limb (35 and 37% increase). Together, these data suggest a role for FAT/CD36 in mitochondrial long chain fatty acid uptake and demonstrate system flexibility to match FAT/CD36 mitochondrial content with an increased capacity for fatty acid oxidation, possibly involving translocation of FAT/CD36 to the mitochondria.
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Astaxanthin is a natural antioxidant carotenoid that occurs in a wide variety of living organisms. We investigated, for the first time, antihypertensive effects of astaxanthin (ASX-O) in spontaneously hypertensive rats (SHR). Oral administration of ASX-O for 14 d induced a significant reduction in the arterial blood pressure (BP) in SHR but not in normotensive Wistar Kyoto (WKY) strain. The long-term administration of ASX-O (50 mg/kg) for 5 weeks in stroke prone SHR (SHR-SP) induced a significant reduction in the BP. It also delayed the incidence of stroke in the SHR-SP. To investigate the action mechanism of ASX-O, the effects on PGF(2alpha)-induced contractions of rat aorta treated with NG-nitro-L-arginine methyl ester (L-NAME) were studied in vitro. ASX-O (1 to 10 microM) induced vasorelaxation mediated by nitric oxide (NO). The results suggest that the antihypertensive effect of ASX-O may be due to a NO-related mechanism. ASX-O also showed significant neuroprotective effects in ischemic mice, presumably due to its antioxidant potential. Pretreatment of the mice with ASX-O significantly shortened the latency of escaping onto the platform in the Morris water maze learning performance test. In conclusion, these results indicate that astaxanthin can exert beneficial effects in protection against hypertension and stroke and in improving memory in vascular dementia.