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Effects of Coenzyme Q10 on the Expression of Genes involved in Lipid Metabolism in Laying Hens
Abstract
The aim of this study was to investigate the expression patterns of key genes involved in lipid metabolism in response to dietary Coenzyme Q10 (CoQ10) in hens. A total of 36 forty week-old Lohmann Brown were randomly allocated into 3 groups consisting of 4 replicates of 3 birds. Laying hens were subjected to one of following treatments: Control (BD, basal diet), T1 (BD+ CoQ10 100 mg/kg diet) and T2 (BD+ micellar of CoQ10 100 mg/kg diet). Birds were fed ad libitum a basal diet or the basal diet supplemented with CoQ10 for 5 weeks. Total RNA was extracted from the liver for quantitative RT-PCR. The mRNA levels of HMG-CoA reductase(HMGCR) and sterol regulatory element-binding proteins(SREBP)2 were decreased more than 30~50% in the liver of birds fed a basal diet supplemented with CoQ10 (p, XBP1, FASN, and GLUTs in the liver of birds (p
... Although animals can synthesize CoQ10 in many tissues, including the liver and brain (Varela-López et al. 2016), external sources are required to obtain its beneficial properties due to the insufficient quantities synthesized naturally (Hernández-Camacho et al. 2018). On the other hand, it is a low-cost dietary additive with a broad range of beneficial effects (Feher et al. 2007;Shukla and Dubey 2018) that is well known in humans (Varela-López et al. 2016) and poultry (Honda et al. 2010;Honda et al. 2013;Terčič et al. 2011;Jang and Moon 2016;Raeisi-Zeydabad et al. 2017;Omidizadeh et al. 2021). Research conducted by El Basuini et al. (2020) demonstrated that supplementing CoQ10 in the diet of Nile tilapia (Oreochromis niloticus) at concentrations exceeding 20 mg kg −1 enhanced health and growth performance. ...
Background
Coenzyme Q10 (CoQ10) is a natural antioxidant and plays a vital role in the energy production of animal cells; however, its physiological and biochemical properties in fish are unclear.
Objectives
The current experiment was investigated to explore the effects of dietary CoQ10 on growth performance and biochemical and physiological attributes of rainbow trout (Oncorhynchus mykiss).
Methods
A 56‐day feeding trial was conducted with 5 experimental diets supplemented with CoQ10 concentrations at 0, 25, 50, 100 and 200 mg kg⁻¹ of diet and fed to 400 rainbow trout (10 ± 0.1 g, initial body weight).
Results
Dietary supplementation with CoQ10, especially at the highest dietary level, significantly improved the feed conversion ratio, final body weight and lipid and protein efficiency ratio of fish (p < 0.05). Moreover, the fish carcass protein and lipid content significantly increased with supplementation of 200 mg CoQ10 kg⁻¹ diet (p < 0.05). The blood serum levels of triglycerides (TGs), cholesterol (CHO) and uric acid significantly reduced, whereas albumin, total protein, high‐density lipoprotein and lymphocyte count increased with supplementation of 200 mg CoQ10 kg⁻¹ diet (p < 0.05). Administration of 100 mg CoQ10 kg⁻¹ diet significantly reduced the liver gene expression of sterol regulatory element‐binding protein1 (SREBP1), whereas supplementation with 200 mg CoQ10 kg⁻¹ diet increased muscle gene expression of SREBP1 (p < 0.05). However, there were negative associations and correlations between blood TGs and CHO levels with liver and muscle SREBP1 gene expression.
Conclusions
Overall, dietary supplementation of CoQ10, particularly at the levels of 100–200 mg kg⁻¹ of diet, can improve growth performance and health in rainbow trout by modifying blood metabolites and SREBP1 gene expression.
... 특히 생산성 향상을 위 해 고도로 육종된 산란계의 경우 지방간 현상이 빈발하여 간 조직의 산화적 스트레스가 매우 심각하다 (Julian, 2005;Trott et al., 2014;Lin et al., 2021). 따라서 산란계에 CoQ10 을 급여할 경우 체 조직의 미토콘드리아 기능과 항산화 작 용의 증진으로 대사작용으로 발생되는 산화 스트레스부터 신체를 방어하는 중요한 역할을 기대할 수 있다 (Krizman et al., 2013;Jang and Moon, 2016). 육용종계 암탉에서도 CoQ10 급여 시 간 기능 장애와 체 지방을 감소시켜 미토콘 드리아 대사 작용이 활성화되는 것으로 보고되었다 (Sharideh et al., 2020). ...
The knowledge of coenzyme Q levels in tissues, organs, and subcellular compartments is of outstanding interest. A wide amount of data regarding coenzyme Q distribution and occurrence was collected in the last decades; nevertheless the data are often hard to compare because of the different extraction methods and different analytical techniques used. We have undertaken a systematic study for detecting the ubiquinone content in subcellular compartments, cells, and whole-tissue homogenates by a previously standardized HPLC method performed after an extraction procedure identical for all samples. It was confirmed that the major coenzyme Q homologue in rat tissues is coenzyme Q9; however, it was pointed out that all the rodents samples tested contain more than one coenzyme Q homologue. The coenzyme Q homologue distribution is tissue dependent with relatively high coenzyme Q10 content in brain mitochondria, irrespective of the rat strain used. There is no constant relationship of the coenzyme Q content in mitochondria and microsomes fractions. Most organisms tested (including other mammals, bird and fish specimens) have only coenzyme Q10, while the protozoan Tetrahymena pyriformis contains only coenzyme Q8.
Because egg yolk has a high cholesterol concentration, limited egg consumption is often suggested to help prevent ischemic heart disease (IHD).
We epidemiologically examined the validity of this recommendation.
We analyzed the relations of egg consumption to serum cholesterol and cause-specific and all-cause mortality by using the NIPPON DATA80 (National Integrated Project for Prospective Observation of Non-communicable Disease And its Trends in the Aged, 1980) database. At the baseline examination in 1980, a nutritional survey was performed by using the food-frequency method in Japanese subjects aged > or =30 y. We followed 5186 women and 4077 men for 14 y.
The subjects were categorized into 5 egg consumption groups on the basis of their responses to a questionnaire (> or =2/d, 1/d, 1/2 d, 1-2/wk, and seldom). There were 69, 1396, 1667, 1742, and 315 women in each of the 5 groups, respectively. Age-adjusted total cholesterol (5.21, 5.04, 4.95, 4.91, and 4.92 mmol/L in the 5 egg consumption categories, respectively) was related to egg consumption (P < 0.0001, analysis of covariance). In women, unadjusted IHD mortality and all-cause mortality differed significantly between the groups [IHD mortality: 1.1, 0.5, 0.4, 0.5, and 2.0 per 1000 person-years, respectively (P = 0.008, chi-square test); all-cause mortality: 14.8, 8.0, 7.5, 7.5, and 14.5 per 1000 person-years, respectively (P < 0.0001, chi-square test)]. In men, egg consumption was not related to age-adjusted total cholesterol. Cox analysis found that, in women, all-cause mortality in the 1-2-eggs/wk group was significantly lower than that in the 1-egg/d group, whereas no such relations were noted in men.
Limiting egg consumption may have some health benefits, at least in women in geographic areas where egg consumption makes a relatively large contribution to total dietary cholesterol intake.
1. Glucose transporter (GLUT) proteins, one of which is the major insulin-responsive transporter GLUT4, play a crucial role in cellular glucose uptake and glucose homeostasis in mammals. The aim of this study was to identify the extent of mRNA expression of GLUT1, GLUT2, GLUT3 and GLUT8 in chickens intrinsically lacking GLUT4. 2. GLUT1 mRNA was detected in most tissues of 3-week-old broiler chickens, with the highest expression measured in brain and adipose tissue. GLUT2 was expressed only in the liver and kidney. GLUT3 was highly expressed in the brain. GLUT8 was expressed ubiquitously, with expression in kidney and adipose tissue relatively higher than that of other tissues. 3. Expression levels of GLUT isoforms 1, 3 and 8 in skeletal muscle tissue were very low compared to the other tissues tested. 4. [3H]Cytochalasin B binding assays on tissue from 3-week-old chickens showed that the number of cytochalasin B binding sites in skeletal muscle plasma membranes was higher than in liver plasma membranes. These results suggest that GLUT proteins and/or GLUT-like proteins that bind cytochalasin B are expressed in chicken skeletal muscles. 5. It is proposed that GLUT expression and glucose transport in chicken tissues are regulated in a manner different from that in mammals.
Available data on the absorption, metabolism and pharmacokinetics of coenzyme Q10 (CoQ10) are reviewed in this paper. CoQ10 has a fundamental role in cellular bioenergetics. CoQ10 is also an important antioxidant. Because of its hydrophobicity and large molecular weight, absorption of dietary CoQ10 is slow and limited. In the case of dietary supplements, solubilized CoQ10 formulations show enhanced bioavailability. The T(max) is around 6 h, with an elimination half-life of about 33 h. The reference intervals for plasma CoQ10 range from 0.40 to 1.91 micromol/l in healthy adults. With CoQ10 supplements there is reasonable correlation between increase in plasma CoQ10 and ingested dose up to a certain point. Animal data show that CoQ10 in large doses is taken up by all tissues including heart and brain mitochondria. This has implications for therapeutic applications in human diseases, and there is evidence for its beneficial effect in cardiovascular and neurodegenerative diseases. CoQ10 has an excellent safety record.
The present study aimed to investigate the effects of lycopene on hepatic metabolic- and immune-related gene expression in laying hens. A total of 48 25-week-old White Leghorn hens were randomly allocated into four groups consisting of four replicates of three birds: control (basal diet), T1 (basal diet + 10 mg/kg of tomato powder-containing lycopene), T2 (basal diet + 10 mg/kg of micelles of tomato powder-containing lycopene), and T3 (basal diet + 10 mg/kg of purified lycopene). Chickens were fed ad libitum for 5 weeks, and then total RNA was extracted from the livers for quantitative RT-PCR analysis. Peroxisome proliferator-activated receptor {\gamma} (PPAR{\gamma}) expression was decreased in the liver of chickens after lycopene supplementation (P target genes including fatty acid binding protein 4 (FABP4) and fatty acids synthase (FASN) in the T2 group (P were also downregulated in hens fed with micellar lycopene (P (TNF-{\alpha}) and interleukin 6 (IL-6) were downregulated by lycopene supplementation (P
Coenzyme Q10 (CoQ10), a potent lipophilic antioxidant, is a naturally occurring compound with a ubiquitous distribution in nature, and CoQ10 is used as a dietary supplement to combat aging. There is evidence that lipid soluble nutrients can be transferred into the egg yolk from the feed in laying hens. It is therefore possible that feeding CoQ10 to laying hens increases the content of CoQ10 in the egg yolk. In the present study, we investigated the effect of dietary CoQ 10 on its content in the egg yolk of laying hens. Twenty 30 weeks-old Boris Brown hens were assigned based on egg production rate and egg weight to 2 groups (10 birds in each group) and fed a diet containing CoQ10 at 0 or 0.8% for 28 days. Dietary CoQ10 did not affect average egg production rate, feed efficiency, egg weight, and egg yolk weight. CoQ10 content in the egg yolk was increased significantly at 7, 14, 21 and 28 days of the experimental period. Hepatic CoQ10 content and plasma very low density lipoprotein y (VLDLy) CoQ10 concentration in 0.8% group were increased significantly compared with those in 0% group. Dietary CoQ10 significantly decreased cholesterol concentration in the egg yolk at 21(st) and 28(th) day of the experimental period. These findings suggest that, in CoQ10-fed laying hens, the increase of hepatic CoQ10 elevates the plasma VLDLy CoQ10 concentration, which in turn results in a high CoQ10 content in the egg yolk of laying hens.
The effects of dietary coenzyme Q10 (CoQ10) on cholesterol metabolism in laying hens were investigated. Dietary CoQ10 significantly reduced egg yolk cholesterol content and suppressed hepatic hydroxymethylglutaryl-CoA reductase (HMGR) activity. It is therefore likely that CoQ10 acts as an HMGR inhibitor in the livers of laying hens, which in turn results in a reduction in egg-yolk cholesterol.
The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-DeltaDeltaCr) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-DeltaDeltaCr) method. In addition, we present the derivation and applications of two variations of the 2(-DeltaDeltaCr) method that may be useful in the analysis of real-time, quantitative PCR data. (C) 2001 Elsevier science.
Coenzyme Q10 (CoQ10), a potent lipophilic antioxidant, is a naturally occurring compound with a ubiquitous distribution in nature and is used as a dietary supplement to combat aging. In rats, there is evidence that coenzyme Q9, major coenzyme Q homologue in rodents, suppresses hepatic cholestcrogenesis and decreases plasma total cholesterol concentration. In this study, we investigated the effect of dietary CoQ10 on cholesterol metabolism in growing chickens. The supplementation of CoQ10 in a diet significantly decreased the total cholesterol levels in the liver and plasma. Plasma very low density lipoprotein (VLDL) cholesterol concentration was significantly decreased by dietary CoQ10. The enzymatic activity of hepatic hydroxymethylglutaryl-coenzyme A reductase (HMGR), the rate-limiting enzyme of the cholesterol synthetic pathway, was significantly decreased by dietary CoQ10, whereas the mRNA level of HMGR was not affected. These findings suggest that dietary CoQ10 suppresses hepatic cholesterogenesis by the inhibition of HMGR activity at the posttranscriptional level in chickens, which in turn decreases plasma VLDL cholesterol concentration.
The aim of this study was to analyze the expression patterns of key genes involved in lipid metabolism in response to short term fasting in chicks (Gallus gallus). The mRNA level of the genes was analyzed after 0, 2, and 4h of fasting in the liver and white adipose tissue. In the liver, the mRNA level of peroxisome proliferator-activated receptor α was significantly increased after 2h of fasting. The mRNA levels of carnitine palmitoyltransferase 1a and acyl-CoA oxidase were significantly increased after 4h of fasting. In contrast, the mRNA levels of sterol regulatory element-binding protein 1, acetyl-CoA carboxylase α, and fatty acid synthase were significantly decreased after 4h of fasting. The mRNA levels of cholesterol metabolism-related genes such as 3-hydroxy-3-methylglutaryl-CoA reductase and cholesterol 7α-hydroxylase were significantly decreased after 4h of fasting. In the white adipose tissue, the mRNA level of adipose triglyceride lipase was significantly increased after 4h of fasting. In contrast, the mRNA levels of peroxisome proliferator-activated receptor γ and lipoprotein lipase were significantly decreased after 4h of fasting. These results demonstrated that the gene expression of lipid metabolism-related genes is regulated by short term fasting in both the liver and WAT in chicks.
1.1. The concentration of liver ubiquinone increased progressively with the time of feeding ubiquinone, and this increase was reflected in all the cell fractions.2.2. Inhibition of sterol synthesis by ubiquinone was exerted only in the liver, not in the kidney or intestine.3.3. Extending the period of feeding ubiquinone or increasing the concentration of ubiquinone fed had no effect on the extent of inhibition.4.4. Inhibition was found to be specific to ubiquinone-9, the natural major homologue in the rat liver; other homologues were ineffective.5.5. The site of inhibition by ubiquinone was indicated to be between acetyl-CoA and mevalonate, since there was no change in fatty acid and ketone body synthesis in ubiquinone-fed animals as compared to normal animals.
Liver X receptors (LXRs) are members of the nuclear receptor family of transcription factors. They play a crucial role in lipid metabolism processes such as bile acid and fatty acid synthesis, as well as minor or limited roles in the regulation of cholesterol synthesis and uptake in mammals. In avian species, however, little is known about the role of LXRs except for the fact that they are involved in the stimulation of fatty acid synthesis. In this study, we characterize the expression profile of genes related to bile acid, cholesterol, and fatty acid synthesis and VLDL secretion in chicken primary hepatocytes treated with T0901317, a synthetic agonist of LXR. The activity of chicken cholesterol 7α hydroxylase (CYP7A1), a key enzyme in bile acid synthesis, mRNA expression, and bile acid excretion, was stimulated by supplementation of the culture medium with a low concentration (0.01 μM) of T0901317. In contrast, the levels of sterol regulatory element binding protein (SREBP)-1, fatty acid synthase mRNA, and VLDL-triacylglycerol in cells cultured in the presence of a high concentration (10 μM) of T0901317 were higher than those cultured in zero or low concentrations of T0901317. These results suggest that cellular responses to this LXR agonist were similar to those present in mammals. A novel finding of this study concerned changes to the regulation of cholesterol synthesis and uptake in chicken hepatocytes treated with T0901317. Levels of SREBP-2,3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) and low-density lipoprotein receptor (LDLr) mRNA expression increased as a function of increasing T0901317 (up to 1.0 μM), but remained similar to those in cells cultured under control conditions when the concentration of T0901317 was increased to 10 μM. These results suggest that LXRs play an important role in cholesterol synthesis and uptake in chicken hepatocytes and, as such, differ to findings in mammals where the effect of LXR agonists on cholesterol synthesis plays only a minor role in the regulation of cellular sterol homeostasis.
The vital role of coenzyme Q in mitochondrial electron transfer and its regulation, and in energy conservation, is well established. However, the role of coenzyme Q in free oxyradical formation and as an antioxidant remains controversial. Demonstration of the existence of the semiquinone form of coenzyme Q during electron transport, coupled with recent evidence that hydrogen peroxide (but not molecular oxygen) may act as an oxidant of the semiquinone, suggests that the highly reactive OH. radical may be formed from the semiquinone. On the other hand, data exist implicating the Fe-S species as the source of electron transfer chain, free radical production. Additional data exist suggesting instead that the unpaired electron of the coenzyme Q semiquinone most likely dismutases superoxide radicals. These concepts and those arising from observations at several levels of organization including subcellular systems, intact animals, and human subjects in the clinical setting, supporting the concept of reduced coenzyme Q as an antioxidant, will be presented. The results of recent studies on the interaction between the two-electron quinone reductase--DT diaphorase and coenzyme Q10 will be presented. The possibility that superoxide dismutase may interact with reduced coenzyme Q, in conjunction with DT diaphorase inhibiting its autoxidation, will be described. The regulation of cellular coenzyme Q concentrations during oxidative stress accompanying aerobic exercise, resulting in increased protection from free radical damage, will also be presented.
The distribution and biosynthesis of ubiquinone were investigated in vivo in rats and using liver slices. In addition to mitochondria, Golgi vesicles and lysosomes also contain large amounts of this lipid, and even the plasma membrane, peroxisomes and microsomes demonstrate easily measurable amounts. The spectral and chromatographic properties of microsomal ubiquinone were identical to those of its mitochondrial counterpart. When pentane was used to deplete beef heart submitochondrial particles of ubiquinone, NADH and succinate oxidase activities could be restored by reincorporation of microsomal ubiquinone. Injection of [3H]mevalonate into the portal vein of rats and incubation of liver slices with [3H]mevalonate and [3H]- and [14C]tyrosine demonstrated that labeling of mitochondrial ubiquinone was initially much lower than labeling of the microsomal lipid. Furthermore, intraportal injection of [3H]mevalonate resulted in the rapid appearance of labeled ubiquinone in the blood. These results indicate that ubiquinone is synthesized not only in mitochondria, but also on the endoplasmic reticulum of rat liver.
1.1. Isolated adipose tissue of the domestic chick (Gallus domesticus) has a low lipogenic capacity.2.2. This tissue utilizes more acetate and pyruvate than glucose for fatty acid synthesis.3.3. In the presence of unlabelled glucose, insulin did not stimulate the incorporation of acetate-1-C14 or pyruvate-2-C14 into fatty acids, but stimulated the incorporation of glucose-U-C14 into glyceride-glycerol.4.4. The activity of the pentose cycle dehydrogenase enzymes is low in both chick liver and adipose tissue homogenates.5.5. Malic enzyme activity is high in chick liver homogenates and may be a primary source of reducing equivalents for lipid synthesis in this organ.
1. The mean incidence of deaths from ascites in the UK in 1993 was 1.4% (0.7% in 1991 and 0.9% in 1992) and 0.8% from sudden death syndrome (SDS). In total, the economic loss to the UK Broiler Industry in 1993 as a result of these 2 conditions was 24 Pounds M. 2. Clear geographical differences emerged in the occurrence of ascites, with, not only the lowest incidences being observed in Northern Ireland, but also the peak of the mortality from ascites occurring much later in the rearing cycle than in other regions on the mainland. 3. In all regions the incidence of SDS was lower than that of ascites but the reason for this disparity remains to be established. 4. Some of the variables associated with the road transportation of day-old chicks from the hatchery to the farm appeared to influence the incidence of ascites. These included distance or time travelled, stocking density, internal lorry temperature and the length of time the lorry was heated before transport as well as the time the shed was heated before chick arrival. Temperature was also an important factor during growth (brooding and finishing). 5. Negative pressure-powered ventilation was preferred in most organisations but more ascites was seen with positive pressure ventilation. However, the lowest incidence of ascites occurred with natural ventilation. There was more ascites relative to shed orientation when the wind direction was from the west compared to the east. 6. This survey identifies the extent of the problem of broiler ascites in the UK and also highlights the importance of good management control of day-old chicks, not only following placement, but even before their arrival on the farm.
The patterns of Glut1 and Glut3 glucose transporter protein and mRNA expression were assessed during embryogenesis of chicken brain and skeletal muscle, Glut4 protein levels were also evaluated in skeletal muscle and heart, and Glut1 was examined in the developing heart and liver. Glut1 protein expression was detectable throughout brain ontogeny but was highest during early development. Glut1 mRNA levels in the brain remained very high throughout development. Glut3 protein was highest very early and very late and mRNA was highest during the last half of development. In embryonic skeletal muscle, the levels of Glut1 and Glut3 proteins and mRNA were highest very early, and declined severely by mid-development. Glut1 protein and mRNA in the heart also peaked early and then decreased steadily. Although Glut1 mRNA levels were consistently high in the embryonic liver, Glut1 protein expression was not detected. These results suggest that (1) Glut1 is developmentally regulated in chick brain, skeletal muscle, and heart, (2) Glut1 mRNA is present in liver but does not appear to be translated, (3) Glut3 in brain increases developmentally but is virtually absent in muscle, and (4) Glut4 protein and mRNA appear to be absent from chick heart and skeletal muscle.
The two most commonly used methods to analyze data from real-time, quantitative PCR experiments are absolute quantification and relative quantification. Absolute quantification determines the input copy number, usually by relating the PCR signal to a standard curve. Relative quantification relates the PCR signal of the target transcript in a treatment group to that of another sample such as an untreated control. The 2(-Delta Delta C(T)) method is a convenient way to analyze the relative changes in gene expression from real-time quantitative PCR experiments. The purpose of this report is to present the derivation, assumptions, and applications of the 2(-Delta Delta C(T)) method. In addition, we present the derivation and applications of two variations of the 2(-Delta Delta C(T)) method that may be useful in the analysis of real-time, quantitative PCR data.
The regulation of hepatic glucose metabolism has a key role in whole-body energy metabolism, since the liver is able to store (glycogen synthesis, lipogenesis) and to produce (glycogenolysis, gluconeogenesis) glucose. These pathways are regulated at several levels, including a transcriptional level, since many of the metabolism-related genes are expressed according to the quantity and quality of nutrients. Recent advances have been made in the understanding of the regulation of hepatic glycolytic, lipogenic and gluconeogenic gene expression by pancreatic hormones, insulin and glucagon and glucose. Here we review the role of the transcription factors forkhead and sterol regulatory element binding protein-1c in the inductive and repressive effects of insulin on hepatic gene expression, and the pathway that leads from glucose to gene regulation with the recently discovered carbohydrate response element binding protein. We discuss how these transcription factors are integrated in a regulatory network that allows a fine tuning of hepatic glucose storage or production, and their potential importance in metabolic diseases.
Ubiquinone (coenzyme Q10), in addition to its function as an electron and proton carrier in mitochondrial electron transport coupled to ATP synthesis, acts in its reduced form (ubiquinol) as an antioxidant, inhibiting lipid peroxidation in biological membranes and protecting mitochondrial inner-membrane proteins and DNA against oxidative damage accompanying lipid peroxidation. Tissue ubiquinone levels are subject to regulation by physiological factors that are related to the oxidative activity of the organism: they increase under the influence of oxidative stress, e.g. physical exercise, cold adaptation, thyroid hormone treatment, and decrease during aging. In the present study, coenzyme Q homologues were separated and quantified in the brains of mice, rats, rabbits, and chickens using high-performance liquid chromatography. In addition, the coenzyme Q homologues were measured in cells such as NG-108, PC-12, rat fetal brain cells and human SHSY-5Y and monocytes. In general, Q1 content was the lowest among the coenzyme homologues quantified in the brain. Q9 was not detectable in the brains of chickens and rabbits, but was present in the brains of rats and mice. Q9 was also not detected in human cell lines SHSY-5Y and monocytes. Q10 was detected in the brains of mice, rats, rabbits, and chickens and in cell lines. Since both coenzyme Q and vitamin E are antioxidants, and coenzyme Q recycles vitamins E and C, vitamin E was also quantified in mice brain using HPLC-electrochemical detector (ECD). The quantity of vitamin E was lowest in the substantia nigra compared with the other brain regions. This finding is crucial in elucidating ubiquinone function in bioenergetics; in preventing free radical generation, lipid peroxidation, and apoptosis in the brain; and as a potential compound in treating various neurodegenerative disorders.
Peroxisome proliferator-activated receptor-gamma (PPARgamma) is considered to be one of the master regulators of adipocyte differentiation. PPARgamma2 is abundantly expressed in mature adipocytes and is elevated in the livers of animals that develop fatty livers. The aim of this study was to determine the ability of PPARgamma2 to induce lipid accumulation in hepatocytes and to delineate molecular mechanisms driving this process. The hepatic cell line AML-12 was used to generate a cell line stably expressing PPARgamma2. Oil Red O staining revealed that PPARgamma2 induces lipid accumulation in hepatocytes. This phenotype is accompanied by a selective upregulation of several adipogenic and lipogenic genes including adipose differentiation-related protein (ADRP), adipocyte fatty acid-binding protein 4, sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FAS), and acetyl-CoA carboxylase, genes whose expression levels are known to increase in steatotic livers of ob/ob mice. Furthermore, the PPARgamma2-regulated induction of both SREBP-1 and FAS parallels an increase in de novo triacylglycerol synthesis in hepatocytes. Triacylglycerol synthesis and lipid accumulation are further enhanced by culturing hepatocytes with troglitazone in the absence of exogenous lipids. These results correspond with an increase in the lipid droplet protein, ADRP, and the data demonstrate that ADRP functions to coat lipid droplets in hepatocytes as observed by confocal microscopy. Taken together, these observations propose a role for PPARgamma2 as an inducer of steatosis in hepatocytes and suggest that this phenomenon occurs through an induction of pathways regulating de novo lipid synthesis.
Coenzyme Q10 is an essential cofactor in the electron transport chain and serves as an important antioxidant in both mitochondria and lipid membranes. CoQ10 is also an obligatory cofactor for the function of uncoupling proteins. Furthermore, dietary supplementation affecting CoQ10 levels has been shown in a number of organisms to cause multiple phenotypic effects. However, the molecular mechanisms to explain pleiotrophic effects of CoQ10 are not clear yet and it is likely that CoQ10 targets the expression of multiple genes. We therefore utilized gene expression profiling based on human oligonucleotide sequences to examine the expression in the human intestinal cell line CaCo-2 in relation to CoQ10 treatment. CoQ10 caused an increased expression of 694 genes at threshold-factor of 2.0 or more. Only one gene was down-regulated 1.5-2-fold. Real-time RT-PCR confirmed the differential expression for seven selected target genes. The identified genes encode proteins involved in cell signalling (n = 79), intermediary metabolism (n = 58), transport (n = 47), transcription control (n = 32), disease mutation (n = 24), phosphorylation (n = 19), embryonal development (n = 13) and binding (n = 9). In conclusion, these findings indicate a prominent role of CoQ10 as a potent gene regulator. The presently identified comprehensive list of genes regulated by CoQ10 may be used for further studies to identify the molecular mechanism of CoQ10 on gene expression.
1. One hundred and sixty 1-d-old Arbor Acre male broiler chicks were fed with maize-soybean based diets for 6 weeks in a 2 x 2 factorial experiment. The factors were CoQ10 supplementation (0 or 40 mg/kg) and Escherichia coli lipopolysaccharide (LPS) challenge (LPS or saline). 2. CoQ10 was supplemented from d 1. From d 18, the chickens received three weekly i.p. injections of LPS (1.0 mg/kg BW) or an equivalent amount of sterile saline as control. From d 10 on, all chickens were exposed to low ambient temperature (12 to 15 degrees C) to induce ascites. 3. The blood packed cell volume and ascites heart index of broiler chickens were reduced by dietary CoQ10 supplementation. Mitochondrial State 3 and State 4 respiration, respiratory control ratio and phosphate oxygen ratio were not changed, but H+/site stoichiometry of complex II + III was elevated by dietary CoQ10 supplementation. 4. Cytochrome c oxidase and H+-ATPase activity were increased by CoQ10 supplementation, whereas NADH cytochrome c reductase and succinate cytochrome c reductase were not influenced. Mitochondrial anti-ROS capability was increased and malondialdehyde content was decreased by CoQ10 supplementation. 5. The work suggested that dietary CoQ10 supplementation could reduce broiler chickens' susceptibility to ascites, which might be the result of improving hepatic mitochondrial function, some respiratory chain-related enzymes activities and mitochondrial antioxidative capability.
Although coenzyme Q10 (CoQ10) is a component of the oxidative phosphorylation process in mitochondria that converts the energy in carbohydrates and fatty acids into ATP to drive cellular machinery and synthesis, its effect in type I diabetes is not clear. We have studied the effect of 4 wk of treatment with CoQ10 (10 mg/kg, ip, daily) in streptozotocin (STZ)-induced (40 mg/kg, iv in adult rats) type I diabetes rat models. Treatment with CoQ10 produced a significant decrease in elevated levels of glucose, cholesterol, triglycerides, very-low-density lipoprotein, low-density lipoprotein, and atherogenic index and increased high-density lipoprotein cholesterol levels in diabetic rats. CoQ10 treatment significantly decreased the area under the curve over 120 min for glucose in diabetic rats, without affecting serum insulin levels and the area under the curve over 120 min for insulin in diabetic rats. CoQ10 treatment also reduced lipid peroxidation and increased antioxidant parameters like superoxide dismutase, catalase, and glutathione in the liver homogenates of diabetic rats. CoQ10 also lowered the elevated blood pressure in diabetic rats. In conclusion, CoQ10 treatment significantly improved deranged carbohydrate and lipid metabolism of experimental chemically induced diabetes in rats. The mechanism of its beneficial effect appears to be its antioxidant property.
As a result of a hereditable point mutation in the oocyte very low density lipoprotein (VLDL) receptor, sexually mature restricted ovulator (RO) female chickens (Gallus gallus), first described as a non-laying strain, exhibit endogenous hyperlipidemia and develop atherosclerotic lesions. In a 20-day study, RO hens and their normolipidemic (NL) siblings were fed either a control diet, or the control diet supplemented with 0.06% atorvastatin (AT), a potent 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) inhibitor. Compared to NL hens, RO birds exhibited greatly elevated baseline plasma total cholesterol (CHOL) and triglyceride (TG) concentrations (1.56 vs. 4.55 g/l and 30.7 vs. 138.4 g/l, respectively). AT attenuated plasma CHOL and TG concentrations by 60.3% and 70.1%, respectively, in NL hens and by 45.1% and 34.3%, respectively, in RO hens. Messenger RNA levels of several key genes involved in hepatic VLDL assembly were suppressed in RO vs. NL hens, but were unaffected by AT. In contrast, AT elevated liver HMGR mRNA levels in NL and RO birds, but only NL hens exhibited an AT-associated increase in hepatic HMGR immunoreactive protein levels. Down-regulation of HMGR gene expression due to higher baseline levels of circulating CHOL may explain why RO birds responded less robustly than NL hens to AT administration.
Dietary carbohydrates regulate hepatic lipogenesis by controlling the expression of critical enzymes in glycolytic and lipogenic
pathways. We found that the transcription factor XBP1, a key regulator of the unfolded protein response, is required for the
unrelated function of normal fatty acid synthesis in the liver. XBP1 protein expression in mice was elevated after feeding
carbohydrates and corresponded with the induction of critical genes involved in fatty acid synthesis. Inducible, selective
deletion of XBP1 in the liver resulted in marked hypocholesterolemia and hypotriglyceridemia, secondary to a decreased production
of lipids from the liver. This phenotype was not accompanied by hepatic steatosis or compromise in protein secretory function.
The identification of XBP1 as a regulator of lipogenesis has important implications for human dyslipidemias.
Egg Science and Technology
- F Cook
- G M Briggs
Cook F, Briggs GM 1977 Egg Science and Technology, second
ed., eds. Stadelman WJ and Cotterill OJ, Avi Publishing
Company, Westport, pp. 92-108.
User's Guide: Statistics Version 6.12 Ed
SAS 1996 User's Guide: Statistics Version 6.12 Ed. SAS Inst.,
Inc., Cary, NC.