Article

Effect of Garcinia cambogia extract on serum leptin and insulin in mice

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  • Yokohama University of Pharmacy
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Abstract

In this study we examined the effects of 3.3% Garcinia cambogia extract on 10% sucrose loading in mice for 4 weeks. Treatment was found to have no effect on body weight, fat pad weight or serum glucose level. On the other hand, serum total cholesterol, triglycerides, NEFA were observed. Levels of serum insulin and leptin, as well as the leptin/WAT ratio, were lower in the treated mice than in the control. These findings suggested that G. cambogia extract efficiently improved glucose metabolism and displayed leptin-like activity.

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... Short-term weight-loss, anti-liver steatosis and lipid-lowering effects of GGG rind extracts have been reported in rodents and humans, showing mild or no side effects when a convenient pharmacological dose was used [8][9][10]. Particularly, the metabolic outcomes described above have been been observed for rodents fed different concentrations of high fat (HF), or high sugar (HS)-based diets, either alone or combined (HFS; "Western") and using different experimental designs [12][13][14][15][16][17][18]. Thus, an objective comparison of GGG's HCA benefits on the metabolic derangements associated with primary disturbances in adipose tissue, promoted by these diets in one single experiment has, to our knowledge, not been addressed. ...
... Briefly, the experimental phases were (A) Acclimatization, in whic rats were housed individually in polycarbonate cages under controlled environmental conditions (22 ± 2 • C, relative humidity 45-60%, 12 h light to dark cycles) and fed with a standard rodent diet and water ad libitum for three days; (B) Obesity induction, in which animals were assigned to a normocaloric ("control", 3.5 kcal/g; n = 5) growth diet AIN-93M [19] or a hypercaloric (5.2 kcal/g; 61.2% energy from fat: soybean oil (10%) and lard (90%); n = 30) diet with 1% cholesterol (mimicking a D12492 diet; Research Diets, Inc., New Brunswick, NJ, USA) which was maintained for five more weeks in order to develop obesity + mild dyslipidemia in the hypercaloric group [20]; and (C) Bioassay, in which obese rats were randomly assigned to one of six hypercaloric diets (4.1 kcal/g), either alone (groups: HF, HS, HFS) or supplemented (groups: HF+, HS+, HFS+) with a GGG rind extract. The amount of GGG rind extract added (5.9 g/100 g diet, 60% HCA) was selected to maximize the average intake of HCA [12][13][14][15][16][17][18] in order to observe clinical benefits without causing adverse effects [8][9][10]. The groups maintained the assigned diet for eleven more weeks, while rats fed the "control" diet kept the same normocaloric diet without GGG supplementation. ...
... g/day of GGG rind extract. Translating research findings from murine bioassays into human trajectories of disease and therapeutics has been one of the major challenges of translational medicine, but, from an ethical point of view, pharmacological testing in murine models precedes clinical trials in humans, and for GGG rind extracts, the evaluation of its pharmacological action, nutraceutical effects, and toxicity in murine models has been useful for this effect [12][13][14][15][16][17][18]. Nonetheless, all findings reported in this study should be further assessed in an intervention trial in humans. ...
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Garcinia gummi-gutta (GGG) rind extract is effective for reducing appetite, body weight and adiposity of obese rodents fed high-fat (HF), high-sugar (HS) or high fat/sugar (HFS)-based diets, but these effects have not been simultaneously evaluated. Thirty obese (~425 g) male Wistar rats were fed for eleven weeks with six hypercaloric diets (4.1 kcal/g; five rats/diet) non-supplemented (HF, HS, HFS), or supplemented (HF+, HS+, HFS+) with GGG extract (5.9%), while rats from the control group (375 g) were fed a normocaloric diet (3.5 kcal/g). Body weight, dietary intake, body fat distribution, and histological and biochemical parameters were recorded. Compared to control rats, non-supplemented and supplemented groups consumed significantly less food (14.3% and 24.6% (−4.3 g/day), respectively) (p < 0.05). Weight loss was greater in the HF+ group (35-52 g), which consumed 1.9 times less food than the HS+ or HFS+ fed groups. The HF and HFS groups showed 40% less plasma triacylglycerides and lower glucose levels compared to the HF+. GGG-supplemented diets were associated with lower ketonuria. The HF+ diet was associated with the best anti-adiposity effect (as measured with the dual X-ray absorptiometry (DXA) and Soxhlet methods). The severity of hepatocyte lipidosis was HF > control > HF+, and no signs of toxicity in the testes were observed. The results indicate that GGG is more effective when co-administered with HF diets in obese rats.
... Many Garcinia species like Garcinia cambogia (Hayamizu et al. 2003;Asghar et al. 2007;Wielinga et al. 2005;Cheng et al. 2012), Garcinia indica (Sasaki et al. 2007;Kirana & Srinivasan 2010;Yamaguchi et al. 2000), Garcinia mangosteen (Ryu et al. 2011;Nelli et al. 2013), and Garcinia kola (Adaramoye 2012) have been reported to possess anti-diabetic and anti-oxidant properties. However, there are still no scientific reports on the anti-diabetic potential of G. xanthochymus seed extracts. ...
... species have been used for hundreds of years as traditional medicines (Chinese, Indian, and Thai) for various medicinal practices. Various Garcinia species like G. cambogia(Hayamizu et al. 2003;Asghar et al. 2007;Wielinga et al. 2005;Cheng et al. 2012), G. indica(Sasaki et al. 2007;Kirana and Srinivasan 2010;Yamaguchi et al. 2000), G. mangosteen(Ryu et al. 2011;Nelli et al. 2013), and G. kola(Adaramoye 2012) have shown to possess anti- ...
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In the present study, extracts of Garcinia xanthochymus seeds were used to determine anti-diabetic, anti-oxidant, and biochemical activities in alloxan-induced diabetic mice. Of the petroleum ether (G. xanthochymus petroleum ether extract (GXSPE)) and methanol (G. xanthochymus methanol extract (GXSME)) seed extracts, 100 and 200 mg/kg were used and compared with normal, diabetic, and glibenclamide groups for various activities. The parameters like blood glucose, body weight, serum biochemicals, serum enzymes, and anti-oxidative enzymes in different groups were monitored at regular intervals. The extracts produced a dose-dependent response for blood glucose levels and associated serum biochemicals, serum enzymes, and anti-oxidative enzymes compared to the diabetic control groups. The high-pressure liquid chromatography (HPLC) analysis revealed the presence of phenolic compounds especially gallic acid, 4-hydroxybenzoic acid, and tannic acid, which have an important role in anti-diabetic action. Thus, this study points out the strong anti-diabetic, anti-oxidant, and biochemical activity of G. xanthochymus seeds. Hence, it can be used for the development of an effective herbal pharmaceutical drug for curing diabetes.
... A study has indicated that insulin indirectly increases leptin release by increasing the metabolism of nutrients, specially glucose, in adipocytes (42). Consistently, our results also showed that increased leptin release is associated with increased insulin release in the animals fed with high sucrose diet (43). An experimental study has shown that the olive seed extract reduces the expression of the adipogenic peroxisome proliferator-activated receptor-g (PPARg) and leptin genes in mouse fibroblasts (27). ...
... In addition, Maalej et al have reported that phenolic compounds obtained from olive fruit extract has a protective effect on deltamethrin-induced hepatotoxicity by reducing apoptosis and inflammation (52). Hydroxytyrosol decreases lipid levels (43) and blood cholesterol (54) in rats fed with cholesterol diet and streptozotocin-induced diabetic rats. ...
Article
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Background: Metabolic syndrome (MetS) increases the risk of diabetes. Olea europaea fruit exerts protective effects on metabolic disorders. Therefore, the aim of the present study was to investigate the effect of O. europaea fruit extracts on sucrose-induced MetS in rats. Methods: Male adult Wistar rats (200±50 g, n=32) were randomly divided into four groups (n=8) consisting of control group, untreated sucrose group (sucrose 50% in drinking water for 10 weeks), sucrose plus aqueous extract of O. europaea fruit treated group (200 mg/kg) and sucrose plus hydroalcoholic extract of O. europaea fruit treated group (200 mg/kg) by gavage for 2 weeks. Body weight, serum glucose, insulin, leptin, lipid profile, homeostatic model assessment of insulin resistance (HOMA-IR) and hepatic enzymes were measured. Data were analyzed by one-way analysis of variance (ANOVA, SPSS, 16.0). P<0.05 was regarded as significance level. Results: The aqueous extract exhibited higher protective effects on serum glucose, insulin and HOMA-IR than hydroalcoholic extract (P<0.05). Body weight, serum glucose, leptin (P<0.01), insulin, triglyceride, very-low-density lipoprotein cholesterol (VLDL-C), HOMA-IR, alkaline phosphatase (ALP), (P<0.001) and aspartate aminotransferase (AST) (P<0.05) significantly elevated but high-density lipoprotein cholesterol (HDL-C) (P<0.05) decreased in the sucrose group. Aqueous extract of O. europaea fruit significantly improved blood glucose, triglyceride, VLDL-C (P<0.01), insulin, HOMA-IR, ALP (P<0.001), body weight, AST and leptin (P<0.05) levels. Hydroalcoholic extract of O. europaea fruit significantly restored insulin, HOMA-IR (P<0.01), ALP (P<0.001), body weight, leptin, VLDL-C, triglyceride, blood glucose and AST (P<0.05). Conclusion: Our results indicated O. europaea fruit extracts could improve metabolic disorders induced by MetS in the rats.
... (-)-Hydroxycitric acid (HCA) is a principal acid in the fruit rinds of Garcinia cambogia (Loon et al., 2000;Lewis and Neelakantan, 1965) which is a competitive inhibitor of ATP-citratelyase, a cytosolic enzyme that catalyses the extramitochondrial cleavage of citrate to oxaloacetate and acetyl-CoA (Sullivan et al., 1977). The action of HCA should reduce the acetyl-CoA pool, thus limiting the availability of two-carbon units required for fatty acid and cholesterol biosynthesis (Hayamizu et al., 2003b). This has led to suggestions that administration of HCA could inhibit lipogenesis. ...
... They found that the mean values of total cholesterol did not change in the Garcinia cambogia group. Hayamizu et al. (2003b) reported that serum total cholesterol levels of dietary Garcinia cambogia-treated (3.3%) mice tended to be lower than those of control mice (P<0.1). Whereas, Koshy et al. (2001) gave Garcinia cambogia at a dose of 1 mg/100 g body weight/day by oro-gastric tube to the rats, and determined that the serum concentration of cholesterol decreased significantly in the experimental animals when compared to the control group. ...
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The aim of the study was to investigate the effect of the antiobesity agent Garcinia cambogia extract, on serum lipoprotein (a), apolipoproteins A1 (apo A1) and B (apo B), and total cholesterol levels in atherogenic diet fed rats. Thirty female, one year old Sprague-Dawley rats were separated to three equal groups. Group 1 (control group) was fed basal diet (2% liquid vegetable oil, 0% cholesterol). The diets of Groups 2 and 3 contained vegetable oil (2% liquid and 5% hydrogenated) and cholesterol (3%) in high levels. 4.5% (w/w) Garcinia cambogia extract was added to the diet of Group 3 after Day 45 up until the end of trial period. Blood samples were withdrawn on Days 0, 45 and 75. Serum lipoprotein (a), apo B, apo A1 and total cholesterol levels were determined by colorimetric methods. Serum lipoprotein (a) and apolipoprotein B levels were not significantly different between groups throughout the study. Serum apo A1 levels increased (P<0.05) towards the end of the study in Groups 2 and 3. Serum total cholesterol levels were significantly higher in Groups 2 and 3 than in the control group on Days 45 and 75. Garcinia cambogia extract did not ave any significant effect on the analysed indices. The rising in serum apo A1 levels in Groups 2 and 3 was surprising, ince apo A1 is a primary protein of high density lipoprotein and is protector from atherosclerosis. In conclusion, a %65 HCA containing diet was insufficient to lower atherosclerotic lipoprotein levels. Therefore, a higher dose of Garciniacambogia extract should be experienced in future studies.
... Obesity, which is defined as an increase of adipose mass resulting from a chronic imbalance between caloric intake and energy expenditure, is a multifactorial condition (Weiser et al., 1997). The intake of fat and energy is included in the problem of excessive energy intake (Hayamizu et al., 2003). Obesity is a serious risk factor that complicates and contributes to serious diseases such as diabetes, cardiovascular disease and hypertension (Brandt et al., 2006). ...
... The reason for the higher triglyceride levels in group 2 was the stimulation of triglyceride synthesis by 3% dietary cholesterol as reported by Fungwe et al. (1993). In the study of Hayamizu et al. (2003), serum triglyceride levels were significantly lower in the Garcinia cambogia group than those of the control mice. However, Brandt et al. (2006) observed that long-term HCA treatment led to several unexpected and deleterious effects on lipid metabolism and no improvement in postprandial plasma triglyceride levels. ...
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The aim of the study was to investigate the preventive effects of dietary Garcinia cambogia extract on lipid metabolism and serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyle transferase (GGT) in rats fed high-lipid diet. Thirty female, one-year-old Sprague-Dawley rats were used and separated into three equal groups. Group 1 (control group) was fed basal diet (2% liquid vegetable oil, 0% cholesterol), while the diets of both group 2 and 3 contained vegetable oil (2% liquid and 5% hydrogenated vegetable oil) and cholesterol (3%). 4.5% (w/w) Garcinia cambogia extract was added to the diet of group 3 from day 45. Blood samples were withdrawn from all rats on days 0, 45 and 75. Serum levels of total protein, LDL-cholesterol and phospholipid were lower in the control group than in the other two groups, and there were no significant differences between these two experimental groups at the end of the study (P<0.05). Serum triglyceride concentrations rose significantly in the Garcinia cambogia- supplemented group (group 3). HDL-cholesterol levels were significantly different between the three groups (P<0.05). The highest levels were in the control group. Serum ALT activities were not significantly different between the groups at the end of the study. Serum AST and GGT activities were significantly lower in the groups 2 and 3 than those in the controls, respectively. Fat feeding caused rising lipid indices in serum, while Garcinia cambogia supplementation to the fatty diet failed to decrease the rise in serum lipid indices in the present dose. The higher doses of Garcinia cambogia extract should be investigated.
... Moreover, in some non-clinical studies in rodents, G. cambogia fruit extracts have also been associated with weight loss and appetite suppression activity, probably as a result of the https://doi.org/10.1016/j.fct.2019.03.051 Received 15 December 2018; Received in revised form 25 March 2019; Accepted 27 March 2019 Abbreviations: AED, antiepileptic drug; AUC, area under the concentration-time curve; AUC 0-24 , AUC from time zero to 24 h; AUC 0-t , AUC from time zero to the last measurable concentration; AUC 0-∞ , AUC from time zero to infinity; AUMC 0-∞ , area under the first moment of the concentration-time curve from zero to infinity; CL/ F, apparent clearance; C max , peak concentration; HPLC-DAD, high-performance liquid chromatography-diode array detection; IS, internal standard; k el , apparent elimination rate constant; LTG, lamotrigine; MEPS, microextraction by packed sorbent; MRT, mean residence time; p.o., per os; t 1/2el , elimination half-life; t max , time to reach peak concentration; V d /F, apparent volume of distribution increase in brain serotonin levels, reduction in plasma insulin levels and inhibition of the enteral absorption of glucose ( Hayamizu et al., 2003;Ohia et al., 2001;Wielinga et al., 2005). Although most studies have shown efficacy on weight loss, in some human studies no significant weight or fat reduction was observed even when high doses of G. cambogia or HCA supplements were used for long periods of time (Kim et al., 2011;Onakpoya et al., 2011;Semwal et al., 2015;Yonei et al., 2008). ...
... The 14-day treatment period with G. cambogia extract did not show a significant effect on the body weight of rats, which was somewhat unexpected given the uses claimed for G. cambogia-containing supplements. However, other non-clinical studies conducted in mice also found no significant effects on the body weight of animals after G. cambogia administration for four ( Hayamizu et al., 2003) and sixteen weeks ( Kim et al., 2013). On the contrary, in the study of Sripradha and Magadi (2015), G. cambogia administered at 400 mg/kg during ten weeks significantly decreased the body weight gain in male Wistar rats fed with high-fat diet. ...
... Fruits from the genus Garcinia are best known for their antibacterial and weight loss effects. Weight loss may be due to leptin-like activity and the resultant decreases in insulin and insulin sensitivity, in addition to appetite suppression [22]. In sucrose-loaded mice fed Garcinia cambogia rind extract, there was a significant decrease in serum insulin levels (3.52 versus 1.83 ng/mL) compared to controls [22]. ...
... Weight loss may be due to leptin-like activity and the resultant decreases in insulin and insulin sensitivity, in addition to appetite suppression [22]. In sucrose-loaded mice fed Garcinia cambogia rind extract, there was a significant decrease in serum insulin levels (3.52 versus 1.83 ng/mL) compared to controls [22]. Male rats consuming a high fat diet showed increased serum leptin levels and decreased glucose intolerance when fed Garcinia cambogia ethanolic extract [65]. ...
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Acne vulgaris affects most people at some point in their lives. Due to unclear etiology, likely with multiple factors, targeted and low-risk treatments have yet to be developed. In this review, we explore the multiple causes of acne and how plant-based foods and supplements can control these. The proposed causative factors include insulin resistance, sex hormone imbalances, inflammation and microbial dysbiosis. There is an emerging body of work on the human gut microbiome and how it mediates feedback between the foods we eat and our bodies. The gut microbiome is also an important mediator of inflammation in the gut and systemically. A low-glycemic load diet, one rich in plant fibers and low in processed foods, has been linked to an improvement in acne, possibly through gut changes or attenuation of insulin levels. Though there is much interest in the human microbiome, there is much more unknown, especially along the gut-skin axis. Collectively, the evidence suggests that approaches such as plant-based foods and supplements may be a viable alternative to the current first line standard of care for moderate acne, which typically includes antibiotics. Though patient compliance with major dietary changes is likely much lower than with medications, it is a treatment avenue that warrants further study and development.
... 32,34,35 (-) Hydroxycitric acid and 2-heptyl acetate, 2-methyl butyl acetate and isoamyl acetate are carboxylic acid derivatives from Garcinia cambogi and Gymnema sylvestre respectively that induce insulin secretion. 35,36 Erulic acid from Curcuma longa activates free radical scavenging activity and insulin secretion. 37 Aloe vera extracts contain leucine, isoleucin and alanine, which trigger insulin secretion. ...
Article
Diabetes Mellitus, characterized by persistent hyperglycaemia, is a heterogeneous group of disorders of multiple aetiologies. It affects the human body at multiple organ levels thus making it difficult to follow a particular line of the treatment protocol and requires a multimodal approach. The increasing medical burden on patients with diabetes-related complications results in an enormous economic burden, which could severely impair global economic growth in the near future. This shows that today’s healthcare system has conventionally been poorly equipped towards confronting the mounting impact of diabetes on a global scale and demands an urgent need for newer and better options. The overall challenge of this field of diabetes treatment is to identify the individualized factors that can lead to improved glycaemic control. Plants are traditionally used worldwide as remedies for diabetes healing. They synthesize a diverse array of biologically active compounds having antidiabetic properties. This review is an endeavour to document the present armamentarium of antidiabetic herbal drug discovery and developments, highlighting mechanism-based antidiabetic properties of over 300 different phytoconstituents of various chemical categories from about 100 different plants modulating different metabolic pathways such as glycolysis, Krebs cycle, gluconeogenesis, glycogen synthesis and degradation, cholesterol synthesis, carbohydrate metabolism as well as peroxisome proliferator activated receptor activation, dipeptidyl peptidase inhibition and free radical scavenging action. The aim is to provide a rich reservoir of pharmacologically established antidiabetic phytoconstituents with specific references to the novel, cost-effective interventions, which might be of relevance to other low-income and middle-income countries of the world.
... G. gummi-gutta also showed effect on reproductive system, lipid peroxidation, blood viscosity, haematology and plasma biochemistry (Semwal et al., 2015). G. gummi-gutta extract has shown significant antidiabetic property by efficiently improving glucose metabolism and displaying leptin like activity (Hayamizu et al., 2003). Remarkable antibacterial effect has been observed for various extracts of G. gummi-gutta (Jacob et al., 2015, Rani and Lawerence, 2015, Maridass et al., 2010. ...
Book
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The plant kingdom represents an extraordinary reservoir of molecules, that can be beneficial to mankind in several ways and currently there is a worldwide interest in the use of natural products, particularly plant derived products. The Western Ghats, one among 36 global biodiversity hotspots, harbors one of the finest tropical forests in the world. A recent enumeration has identified nearly 7500 flowering plants in the Western Ghats, of which more than 1250 are endemic to the region. Literature review revealed that nearly 80% of the endemic flowering plants of the region are hitherto uninvestigated for their chemical constituents, bioactivities or potential utilities. Garcinia species are one among such least explored group of plants, represented by 9 species and 2 varieties in the Western Ghats, of which 7 species and 2 varieties are endemic to the region. The genus Garcinia is important as a source of edible fruits, edible fats like kokum butter, oleoresin and coloring agents, the much valued anti-obesity phytochemical hydroxycitric acid (HCA) and other bioactive compounds like biflavonoids and xanthones. Due to the diversity of natural products and the presence of high value compounds, several industrial sectors like pharmaceutical, nutraceutical, paint and food additives are centred around this potential group of trees. In south India, G. gummi-gutta and G. indica are cultivated for commercial extraction of a variety of products such as bioactive acids, nutraceuticals, fats and condiments. Literature review reveals that out of the nearly 250 Garcinia species, 120 species have so far been investigated for their chemical constituents. Garcinia species are found to be rich sources of structurally diverse secondary metabolites such as xanthones, benzophenones and biflavonoids, in addition to flavonoids, biphenyls, phloroglucinols, depsidones and triterpenoids as minor constituents. Though the Western Ghats has a rich diversity of Garcinia species, only a few species are exploited sustainably for their potential utilities. The rich floristic wealth can be harvested profitably by taking advantage of the developments in phytochemical analytical techniques. Phytochemistry, being an interdisciplinary subject linked to different disciplines, the present book also includes recent research activities in the fields such as botany, pharmacology and plant biotechnology of the genus. It is expected that the effort will open new vistas of knowledge and prove to be an excellent exposition of current research efforts in India in the field of Phytochemistry.
... G. gummi-gutta also showed effect on reproductive system, lipid peroxidation, blood viscosity, haematology and plasma biochemistry (Semwal et al., 2015). G. gummi-gutta extract has shown significant antidiabetic property by efficiently improving glucose metabolism and displaying leptin like activity (Hayamizu et al., 2003). Remarkable antibacterial effect has been observed for various extracts of G. gummi-gutta ( ., 2011). ...
... Thus, (-)-HCA supplementation is expected to alter metabolic pathways. Although some studies have shown (-)-HCA possesses antiobesity activity [36,37] and anti-diabetic activity [38,39], little information is available on whether (-)-HCA affects fat accumulation in broiler chickens through regulation on the energy metabolism. ...
Article
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Background/aims: (-)-Hydroxycitric acid (HCA) had been shown to suppress fat accumulation in animals and humans, while the underlying biochemical mechanism is not fully understood, especially little information is available on whether (-)-HCA regulates energy metabolism and consequently affects fat deposition. Methods: Hepatocytes were cultured for 24 h and then exposed to (-)-HCA (0, 1, 10, 50 µM), enzyme protein content was determined by ELISA; lipid metabolism gene mRNA levels were detected by RT-PCR. Results: (-)-HCA significantly decreased the number and total area of lipid droplets. ATP-citrate lyase, fatty acid synthase and sterol regulatory element binding protein-1c mRNA level were significantly decreased after (-)-HCA treatment, whereas peroxisome proliferator-activated receptor α mRNA level was significantly increased. (-)-HCA significantly decreased ATP-citrate lyase activity and acetyl-CoA content in cytosol, but significantly increased glucose consumption and mitochondrial oxygen consumption rate. (-)-HCA promoted the activity/content of glucokinase, phosphofructokinase-1, pyruvate kinase, pyruvate dehydrogenase, citrate synthase, aconitase, succinate dehydrogenase, malate dehydrogenase, NADH dehydrogenase and ATP synthase remarkably. Conclusions: (-)-HCA decreased lipid droplets accumulation by reducing acetyl-CoA supply, which mainly achieved via inhibition of ATP-citrate lyase, and accelerating energy metabolism in chicken hepatocytes. These results proposed a biochemical mechanism of fat reduction by (-)-HCA in broiler chickens in term of energy metabolism.
... Therefore, some cumulative studies indicated that natural compounds, e.g., rutin, curcumin, antroquinonol, quercetin, and 16-hydroxy-cleroda-3, 13-dien-15, 16-olide (HCD), could inhibit DPP4 activity, such as the inhibitory efficacy of curcumin and quercetin, better than Sitagliptin [36,37,51]. A previous report showed that the extract of the G. cambogia fruit, which contains hydroxycitric acid (HCA), could decrease the serum insulin levels and prolong intestinal tracts to absorb glucose as well as to potentially change incretins (GLP-1, GIP) secretions [10,52]. Taken altogether, the extract of G. cambogia could regulate blood glucose levels, treat metabolic syndromes, and lead to weight loss. ...
Article
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Approximately 400 Garcinia species are distributed around the world. Previous studies have reported the extracts from bark, seed, fruits, peels, leaves, and stems of Garcinia mangostana, G. xanthochymus, and G. cambogia that were used to treat adipogenesis, inflammation, obesity, cancer, cardiovascular diseases, and diabetes. Moreover, the hypoglycemic effects and underlined actions of different species such as G. kola, G. pedunculata, and G. prainiana have been elucidated. However, the anti-hyperglycemia of G. linii remains to be verified in this aspect. In this article, the published literature was collected and reviewed based on the medicinal characteristics of the species Garcinia, particularly in diabetic care to deliberate the known constituents from Garcinia and further focus on and isolate new compounds of G. linii (Taiwan distinctive species) on various hypoglycemic targets including α-amylase, α-glucosidase, 5′-adenosine monophosphate-activated protein kinase (AMPK), insulin receptor kinase, peroxisome proliferator-activated receptor gamma (PPARγ), and dipeptidyl peptidase-4 (DPP-4) via the molecular docking approach with Gold program to explore the potential candidates for anti-diabetic treatments. Accordingly, benzopyrans and triterpenes are postulated to be the active components in G. linii for mediating blood glucose. To further validate the potency of those active components, in vitro enzymatic and cellular function assays with in vivo animal efficacy experiments need to be performed in the near future.
... However, no changes were observed in food intake of rats within the groups receiving the same diets. Hayamizu et al. reported similar findings for the leptin lowering effect of G. cambogia extracts in mice fed a HFD [45]. In their study also, there was a direct correlation between leptin concentration and adiposity. ...
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Background: Morinda citrifolia L. is widely used as a folk medicinal food plant to manage a panoply of diseases, though no concrete reports on its potential anti-obesity activity. This study aimed to evaluate the potential of M. citrifolia leaf extracts (MLE60) in the prevention of weight gain in vivo and establish its phytochemical profile. Design: Male Sprague-Dawley rats were divided into groups based on a normal diet (ND) or high fat diet (HFD), with or without MLE60 supplementation (150 and 350 mg/kg body weight) and assessed for any reduction in weight gain. Plasma leptin, insulin, adiponectin, and ghrelin of all groups were determined. ¹H NMR and LCMS methods were employed for phytochemical profiling of MLE60. Results: The supplementation of MLE60 did not affect food intake indicating that appetite suppression might not be the main anti-obesity mechanism involved. In the treated groups, MLE60 prevented weight gain, most likely through an inhibition of pancreatic and lipoprotein activity with a positive influence on the lipid profiles and a reduction in LDL levels . MLE60 also attenuated visceral fat deposition in treated subjects with improvement in the plasma levels of obesity-linked factors . ¹Spectral analysis showed the presence of several bioactive compounds with rutin being more predominant. Conclusion: MLE60 shows promise as an anti-obesity agents and warrants further research.
... Traditionally, G. cambogia extract has been used to treat tumours, ulcers, haemorrhoids, diarrhoea, dysentery and fever (Jena et al. 2002;Masullo et al. 2008). Regarding its pharmacological activities, G. cambogia has been proved to exhibit anti-ulcer, antitumour, anti-platelets aggregation, anti-hypercholesterolemic, anti-diabetic, cytotoxic, and anti-obesity properties (Koshy et al. 2001;Mahendran et al. 2002;Hayamizu et al. 2003;Kim et al. 2008;dos Reis et al. 2009;Kolodziejczyk et al. 2009;Mazzio & Soliman 2009;Masullo et al. 2014). In today's market, its fruit extract is widely available as anti-obesity products in the form of tablets, capsules and teas. ...
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Species of genus Garcinia are rich sources of bioactive constituents with antimicrobial, anticancer, anti-inflammatory, hepatoprotective and anti-HIV activities. Commercial products of Garcinia cambogia are used as anti-obesity drugs with increasing market demand. Because of the high price of its products, it could be adulterated with similar lower-priced species. This study was designed to develop and validate an accurate and efficient method for the detection of any adulteration (G. indica) in G. cambogia products. For this purpose, high performance liquid chromatography (HPLC) was used to analyze the ethanolic fruit rind extracts of G. cambogia, G. indica, their formulations of 0.5, 1, 2, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90 and 95% G. indica with G. cambogia, and eleven G. cambogia commercial products. The analytical methods were validated by quality assurance parameters of linearity, sensitivity, precision and accuracy. Two marker peaks were detected in G. indica fruit extract, whereas G. cambogia did not show these peaks. The detected peaks were identified as anthocyanins; cyanidin-3-O-sambubioside and cyanidin-3-O-glucoside. In the study to determine the effect of pH and temperature on the stability of its anthocyanins content, HPLC analysis of G. indica extract showed the highest content at pH 1 and 50 °C. Using two different mobile phases, the limits of detection (LOD) for cyanidin-3-O-sambubioside and cyanidin-3-O-glucoside were 0.036 and 0.059, and 0.022 and 0.033 mg/kg, respectively. Furthermore, the inter-day precision (< 3.2%) confirmed that the applied analytical method fulfils the required criteria of Association of Official Analytical Chemists (AOAC). From this study, it was found that the HPLC method used for the detection of adulteration in G. cambogia products is rapid and accurate.
... The result was in agreement with the result of Preuss et al., who reports that after eight weeks groups treated with (−)-HCA showed significant decrease in low density lipoprotein and triglycerides levels than in the placebo group [25]. Haymamizu also reports that serum TG is lower in mice treated with 3.3 % Garcinia cambogia extract [48]. Recently, a double-blind randomized 12 week trial showed significant reductions in total cholesterol and lowdensity lipoprotein cholesterol in the Garcinia cambogia group, compared to the placebo group [49]. ...
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Background Chicken as a delicious food for a long history, and it is well known that excess fat deposition in broiler chickens will not only induced metabolic diseases, but also lead to adverse effect in the consumer’s health. (−)-Hydroxycitric acid (HCA), a major active ingredient of Garcinia Cambogia extracts, had shown to suppress fat accumulation in animals and humans. While, the precise physiological mechanism of HCA has not yet been full clarified, especially its action in broiler chickens. Thus, this study aimed to assess the effect of (−)-HCA on lipid metabolism in broiler chickens. MethodsA total of 120 1-day-old broiler chickens were randomly allocated to four groups, with each group was repeated three times with 10 birds. Birds received a commercial diet supplemented with (−)-HCA at 0, 1000, 2000 or 3000 mg/kg, respectively, for a period of 4 weeks ad libitum. ResultsBody weight (BW) in the 2000 and 3000 mg/kg (−)-HCA groups was significantly decreased (P < 0.05) than that in control group. A significantly decreased of serum triglyceride (TG) and density lipoprotein-cholesterol (LDL-C) content were observed in 3000 mg/kg (−)-HCA group (P < 0.05). Broiler chickens supplmented with 2000 and 3000 mg/kg (−)-HCA had pronouncedly higher hepatic lipase (HL) activity, hepatic glycogen and non-esterified fatty acid (NEFA) contents in liver (P < 0.05). Serum free triiodothyronine (FT3) and thyroxin (T4) contents were significantly higher in 3000 mg/kg (−)-HCA group (P < 0.05) compared with the control group. Supplemental (−)-HCA markedly decreased fatty acid synthase (FAS) and sterol regulatory element binding protein-1c (SREBP-1c) (P < 0.05) mRNA levels, while the mRNA abundance of adenosine 5′-monophosphate-activated protein kinaseβ2 (AMPKβ2) (P < 0.05) was significantly increased. In addition, ATP-citrate lyase (ACLY) mRNA level (P < 0.05) was significantly decreased in broiler chickens supplemented with 3000 mg/kg (−)-HCA. No differences was observed on carnitine palmitoyl transferase-I(CPT-I), while peroxisome proliferators-activated receptor α (PPARα) mRNA level (P < 0.05) was significantly increased in broiler chickens supplemented with 2000 and 3000 mg/kg (−)-HCA. Conclusions Supplemental (−)-HCA inhibited lipogenesis by inhibiting ACLY, SREBP-1c and FAS expression, and accelerated lipolysis through enhancing HL activity and PPARα expression, which eventually led to the reduced abdominal fat deposition in broiler chickens.Graphical abstractMechanism of (−)-HCA effect on hepatic lipids metabolism.
... Extracts from this fruit, which contain hydroxycitric acid (HCA) as the active ingredient, have gained popularity as a dietary supplement to reduce appetite and facilitate weight loss [5], although with limited support for efficacy from short-term clinical trials [6]. Proposed mechanisms of weight loss, based on rodent studies, include a reduction in lipogenesis through inhibition of ATP-citrate-lyase [7], suppression of appetite by elevating brain serotonin levels [8], reductions in plasma insulin levels [9], and inhibition of enteral absorption of glucose [10]. HCA has been shown to delay glucose absorption in rodents, with consequent reductions in peak blood glucose and plasma insulin concentrations in response to intragastric or intraduodenal glucose administration, although the overall area under the curve (AUC) for blood glucose was not affected [10]. ...
Article
Objective: Hydroxycitric acid (HCA), derived from the fruit Garcinia cambogia, reduces the rate of glucose absorption and lowers postprandial glycemia in rodents, but its effect in humans is unknown. The aim of this study was to investigate the effects of small intestinal perfusion with HCA on glucose absorption, as well as the incretin and glycemic responses to a subsequent intraduodenal glucose infusion, in both healthy individuals and patients with type 2 diabetes. Methods: Twelve healthy participants and 8 patients with type 2 diabetes received an intraduodenal infusion of HCA (2800 mg in water) or control (water) over 60 min, followed by an intraduodenal infusion of 60 g glucose over 120 min, in a double-blind, randomized crossover design. In healthy individuals, 5 g 3-O-methylglucose (3-OMG) was co-infused with glucose as a marker of glucose absorption. Blood was sampled frequently. Results: In healthy individuals, blood glucose was lower with HCA than control, both before and during the intraduodenal glucose infusion (P < 0.05 for each). Plasma glucose-dependent insulinotropic polypeptide (GIP; P = 0.01) and glucagon (P = 0.06) were higher with HCA, but there were no differences in plasma glucagon-like peptide (GLP)-1, insulin, or serum 3-OMG concentrations. In patients with type 2 diabetes, blood glucose, and plasma GIP, GLP-1, and insulin did not differ between HCA and control either before or after intraduodenal glucose, but during glucose infusion, plasma glucagon was higher with HCA (P = 0.04). Conclusion: In healthy individuals, small intestinal exposure to HCA resulted in a modest reduction in glycemia and stimulation of plasma GIP and glucagon, but no effect on plasma GLP-1 or insulin, or on glucose absorption. HCA had no effect on glycemia in patients with type 2 diabetes.
... Their findings indicated that upregulation of leptin production is accompanied by enhanced insulin production. They concluded that further studies are required to clarify if the leptinlike activity and its mechanism are effectively due only to the HCA presence or the remaining 40% components in the extract have an important role [75]. In order to study the safety and the influence of Garcinia extract on androgen in humans, Hayamizu et al. ...
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Obesity is a complex disorder of appetite regulation and energy metabolism controlled by specific biological factors. Whenever prevention fails, medicinal treatment of obesity may become an obligation and it is more fruitful when we can acquire the medicinal treatment directly from nature, which is more preferred and healthier rather than going for chemical and surgical treatment. Alternatively, inhibition of carbohydrate to fatty acid conversion reaction can lead to obesity control. This can be done by assay of Hydroxycitric acid [(-)-HCA], which inhibits the formation of ATP-citrate lyase, responsible for lipogenesis. HCA is a derivative of citric acid and found in Garcinia fruit as the principal acid. Many in vitro and in vivo studies have demonstrated that (-)-HCA suppresses the de novo fatty acid synthesis and lipogenesis. However, results from clinical studies showed both negative and positive anti obesity effects of (-)-HCA. In this review paper an attempt has been made to explore and give an insight of (-)-HCA taking account of the literature coverage on speckled topics: Its discovery, properties, extraction and estimation and its significance of role in anti-obesity activity.
... Hayamizu et al. [96] found that 3.3% Garcinia extract with 10% sucrose administered daily to mice for 28 days did not show any effect on body weight, fat pad weight or serum glucose level of mice. However, it decreased the serum insulin level, leptin level and leptin/WAT ratio while improving glucose metabolism. ...
... Hayamizu et al. (27) reported that no statistically significant difference was found between experimental and control groups in the study where mice were given 3.3% Garcinia cambogia with water containing 10% saccharose for 4 weeks. The researchers determined leptin levels as 11.7 ng/ml in the control group and 5.8 ng/ml in the experimental group. ...
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Garcinia cambogia (malabar tamarind, bitter kola) is seen abundantly in the evergreen forests of Konkan in South India. Hydroxycitric acid, mainly obtained from Garcinia cambogia, was identified by the end of the 1960's as a strong competitive inhibitor of the extramitochondrial enzyme adenosine triphosphate citrate lyase. The objective of this study was to present the effect of Garcinia cambogia extract known as weakener on the supportive or preventive hormones (leptin, ghrelin, adiponectin, insulin) of obesity in the rats fed the diet containing hydrogenated-vegetable oil and cholesterol. For this purpose, thirty female 5-6 months-old Sprague-Dawley rats were randomly assigned to three groups. Each group consisted of 10 rats. Group 1 (as control group) was fed with a basal diet while the diets of Groups 2 and 3 contained the hydrogenated-vegetable oil (20%) and cholesterol (1%) beside of other nutrients. Garcinia cambogia extract containing 6% hydroxycitric acid was added to the diet (w/w) of Group 3 after Day 30 up until Day 60. Blood samples were taken from animals on Days 0, 30 and 60 of the trial period. Body weights were weighed in the blood sampling days before sampling. Serum leptin, ghrelin, adiponectin, insülin levels and body weights were not significantly different between groups in the each sampling day. Serum leptin levels were significantly higher on Day 60 than on Days 0 and 30 in Groups 2 and 3. Serum ghrelin levels in Group 3 significantly decreased on Day 30 and significantly increased on Day 60. Serum adiponectin levels in Group 1 were significantly lower on Day 0 than on other days. The levels in Group 3 were significantly higher on Day 60 than on Day 0. The serum insulin levels and body weights were not significantly different between the days in each group. In conclusion, the high lipid diet in doses used in the study (20% hydrogenated-vegetable oil and 1% cholesterol) did not create fat accumulation or obesity in Sprague Dawley rats. Addition of Garcinia cambogia to diet (6%, w/w) of rats fed with the high lipid diet indicated no effect on weight gain. The evidences obtained from this research do not support the role of Garcinia cambogiaplant spreadly used as a weight loss facilitator.
... 32,34,35 (-) Hydroxycitric acid and 2-heptyl acetate, 2-methyl butyl acetate and isoamyl acetate are carboxylic acid derivatives from Garcinia cambogi and Gymnema sylvestre respectively that induce insulin secretion. 35,36 Erulic acid from Curcuma longa activates free radical scavenging activity and insulin secretion. 37 Aloe vera extracts contain leucine, isoleucin and alanine, which trigger insulin secretion. ...
Article
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Diabetes Mellitus, characterized by persistent hyperglycaemia, is a heterogeneous group of disorders of multiple aetiologies. It affects the human body at multiple organ levels thus making it difficult to follow a particular line of the treatment protocol and requires a multimodal approach. The increasing medical burden on patients with diabetes-related complications results in an enormous economic burden, which could severely impair global economic growth in the near future. This shows that today’s healthcare system has conventionally been poorly equipped towards confronting the mounting impact of diabetes on a global scale and demands an urgent need for newer and better options. The overall challenge of this field of diabetes treatment is to identify the individualized factors that can lead to improved glycaemic control. Plants are traditionally used worldwide as remedies for diabetes healing. They synthesize a diverse array of biologically active compounds having antidiabetic properties. This review is an endeavour to document the present armamentarium of antidiabetic herbal drug discovery and developments, highlighting mechanism-based antidiabetic properties of over 300 different phytoconstituents of various chemical categories from about 100 different plants modulating different metabolic pathways such as glycolysis, Krebs cycle, gluconeogenesis, glycogen synthesis and degradation, cholesterol synthesis, carbohydrate metabolism as well as peroxisome proliferator activated receptor activation, dipeptidyl peptidase inhibition and free radical scavenging action. The aim is to provide a rich reservoir of pharmacologically established antidiabetic phytoconstituents with specific references to the novel, cost-effective interventions, which might be of relevance to other low-income and middle-income countries of the world.
... GC is a small fruit with traditional culinary use, and potential medicinal applications. In fact, several clinical interactions of GC have already been documented in the literature, for example, in the context of: appetite control [11,48], neuroprotection [49], lipoproteins and cholesterol control [50], alterations in blood cell count [50], fat mass control [51], glucose metabolism [52], hormones regulation, and interactions with organ system (i.e., kidney) [53]. GC is a source of HCA (structurally related to citric acid), one of the isomers [(−)-hydroxycitric acid], which is thought to help in weight control [54]. ...
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Aims: Use of complementary and alternative medicines (CAMs) during breastfeeding is commonly increasing, mainly due to their presumed higher safety compared to conventional medications. Indeed, CAMs can cause serious adverse effects, and high-quality evidence supporting their use during lactation is limited. In Italy, specific investigations on the attitude of lactating women towards CAMs are lacking. The Herbal supplements in Breastfeeding InvesTigation (HaBIT) aimed to explore the attitudes and knowledge on CAMs among lactating women. Methods: A web-based survey was conducted over a six-year period among lactating women resident in Tuscany (Italy). Data on lactating behavior, CAMs use during pregnancy or breastfeeding, and women knowledge about CAMs' efficacy and safety were collected. Results: 388 lactating women answered the questionnaire; the majority of them were primiparae with high education level. Two-hundred and four women declared to have been CAMs users during breastfeeding. Moreover, the 61 and 48% of subjects reported CAMs use also before and during pregnancy. A significant proportion of subjects were unable to correctly identify the type of CAMs they were using. The 73% of women were convinced that CAMs had higher or comparable safety than conventional medications; nevertheless, 65% of women admitted to have no scientific information about the potential risks of CAMs, and 14 CAMs users reported to have experienced side effects. Conclusions: These results claim the necessity that healthcare providers amplify their role to increase nursing women' awareness about CAMs. Further research is needed to support the evidence base of non-pharmaceutical approaches for symptom control during breastfeeding.
... Antidiabetic Properties Daily supplementation of 3.3% of Garcinia extract diet with 10% sucrose water for 28 days did not show any effect on fat pad mass, body weight, and serum glucose concentrations in mice. However, the treatment reduced serum leptin and insulin concentrations, as well as the leptin-to-white adipose tissue ratio, and it enhanced glucose metabolism [121]. Hydroxycitric acid administration at 500 mg/day for seven days improved the rate of glycogen synthesis, improved post-meal insulin sensitivity, and increased fatty acid translocase/CD36 mRNA expression in exercised human skeletal muscle [122]. ...
Chapter
The genus Garcinia belonging to the Clusiaceae family consists of more than 250 species and is traditionally used for diseases such as dysentery, rheumatism, and inflammation; as an antiparasitic or antimicrobial medication; or as food and flavoring. The genus is native to many countries around the tropical region. Phytochemical analyses have identified the presence of α‐mangostin, γ‐mangostin, hydroxycitric acid, guttiferone A, garcinol, morelloflavone, atroviridin, xanthochymol, kolaviron, and 7‐epiclusianones, among other compounds. These compounds may improve health by their antioxidant, anti‐inflammatory, anti‐obesity, and antiproliferative actions. Metabolic syndrome involves increased oxidative stress and chronic low‐grade inflammation to produce conditions including hypertension, hyperglycemia, abdominal obesity, changes in the plasma lipid profile, and non‐alcoholic fatty liver disease, thereby increasing the risk of stroke, diabetes, and heart disease. This chapter will discuss the potential of the bioactive compounds found in Garcinia species as treatments for metabolic syndrome.
... G. cambogia is used in traditional medicines in many Asian countries to treat various diseases, including intestinal parasites, constipation, bowel complaints, rheumatism, edema, and delayed menstruation [33]. In addition, it possesses anticancer, antidiabetic, antioxidant, anti-inflammatory, antiulcer, antimicrobial, antineoplastic, and gastroprotective activities [34][35][36][37][38][39]. In particular, the extract obtained from G. cambogia fruit peel has been commercialized as a dietary supplement for weight loss [27,40]. ...
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Caffeine, a natural stimulant, is known to be effective for weight loss. On this basis, we screened the arousal-inducing effect of five dietary supplements with a weight loss effect (Garcinia cambogia, Coleus forskohlii, Camellia sinensis L., Irvingia gabonensis, and Malus pumila M.), of which the G. cambogia peel extract (GC) showed a significant arousal-inducing effect in the pentobarbital-induced sleep test in mice. This characteristic of GC was further evaluated by analysis of electroencephalogram and electromyogram in C57L/6N mice, and it was compared to that of the positive control, caffeine. Administration of GC (1500 mg/kg) significantly increased wakefulness and decreased non-rapid eye movement sleep, similar to that of caffeine (25 mg/kg), with GC and caffeine showing a significant increase in wakefulness at 2 and 6 h, respectively. Compared to that of caffeine, the shorter duration of efficacy of GC could be advantageous because of the lower possibility of sleep disturbance. Furthermore, the arousal-inducing effects of GC (1500 mg/kg) and caffeine (25 mg/kg) persisted throughout the chronic (3 weeks) administration study. This study, for the first time, revealed the arousal-inducing effect of GC. Our findings suggest that GC might be a promising natural stimulant with no side effects. In addition, it is preferential to take GC as a dietary supplement for weight loss during the daytime to avoid sleep disturbances owing to its arousal-inducing effect.
... Treatment with 500 mg of HCA, twice a day, promoted weight loss and reduction of fatty mass, visceral fat, total cholesterol, and glycemic profile. Furthermore, an increase of the basal metabolic rate was perceived, independent of sex, age, or bearing hypertension, diabetes mellitus type 2, or dyslipidemia [107]. ...
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Garcinia is a genus of Clusiaceae, distributed throughout tropical Asia, Africa, New Caledonia, Polynesia, and Brazil. Garcinia plants contain a broad range of biologically active metabolites which, in the last few decades, have received considerable attention due to the chemical compositions of their extracts, with compounds which have been shown to have beneficial effects in several diseases. Our work had the objective of reviewing the benefits of five Garcinia species (G. brasiliensis, G. gardneriana, G. pedunculata, G. cambogia, and G. mangstana). These species provide a rich natural source of bioactive compounds with relevant therapeutic properties and anti-inflammatory effects, such as for the treatment of skin disorders, wounds, pain, and infections, having demonstrated antinociceptive, antioxidant, antitumoral, antifungal, anticancer, antihistaminic, antiulcerogenic, antimicrobial, antiviral, vasodilator, hypolipidemic, hepatoprotective, nephroprotective, and cardioprotective properties. This demonstrates the relevance of the genus as a rich source of compounds with valuable therapeutic properties, with potential use in the prevention and treatment of nontransmissible chronic diseases.
... GC is a small fruit with traditional culinary use, and potential medicinal applications. In fact, several clinical interactions of GC have already been documented in the literature, for example, in the context of: appetite control [11,48], neuroprotection [49], lipoproteins and cholesterol control [50], alterations in blood cell count [50], fat mass control [51], glucose metabolism [52], hormones regulation, and interactions with organ system (i.e., kidney) [53]. GC is a source of HCA (structurally related to citric acid), one of the isomers [(−)-hydroxycitric acid], which is thought to help in weight control [54]. ...
Article
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Herbal weight-loss supplements are sold as self-medication products, and are often used under the misconception that their natural origin guarantees their safety. Food supplements are not required to provide any benefit/risk profile evaluation before marketing; however, possible risks associated with use of herbal extracts in food supplements are becoming more and more documented in the literature. Some herbs are listed as the leading cause of herb-induced liver injury, with a severe or potentially lethal clinical course, and unpredictable herb–drug interactions. Garcinia cambogia (GC) extract and GC-containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we present four cases of acute liver failure in women taking GC extract for weight loss, and a literature review of clinical evidences about hepatic toxicity in patients taking dietary supplements containing GC extract.
... The different species of the genus Garcinia are among those herbs widely used for its health benefits as they are rich in phytochemicals. Studies have been reported that the polyphenols isolated from various parts of different species of the genus Garcinia viz., G. gambojia and G. indica, belonging to the family Clusiaceae have antioxidant, anti-obesity, anti-diabetic and other biological properties [8,16,22]. However, the pharmacological activities of G. xanthochymus, a perennial plant native to China and Western Ghats of India, especially in Mangalore and Coorg of the same family is not well studied [9]. ...
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... The different species of the genus Garcinia are among those herbs widely used for its health benefits as they are rich in phytochemicals. Studies have been reported that the polyphenols isolated from various parts of different species of the genus Garcinia viz., G. gambojia and G. indica, belonging to the family Clusiaceae have antioxidant, anti-obesity, anti-diabetic and other biological properties [8,16,22]. However, the pharmacological activities of G. xanthochymus, a perennial plant native to China and Western Ghats of India, especially in Mangalore and Coorg of the same family is not well studied [9]. ...
Article
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Sour mangosteen fruits are good dietary sources of polyphenols with various health benefits. To understand the effects of dietary polyphenols on human health it is essential to determine their stability and fate in the lumen. In the present study, we evaluated the bioaccessibility and bioavailability of fruit peel and rind phenolic extract by in vitro gastrointestinal and in vivo mouse (C57BL/6) models. The results of bioaccessibility of peel showed that epicatechin was highly bioaccessible in oral (97.59% ± 4.87), gastric (82.09% ± 4.01) as well as intestinal (41.60% ± 2.88) phase followed by chlorogenic, syringic and gallic acids whereas, in rind, the gallic acid was highly bioaccessible in oral (66.59% ± 3.93) and gastric (42.89% ± 3.01) phase followed by catechin and chlorogenic acid, however, in intestinal phase catechin (30.99% ± 1.98) was highly bioaccessible followed by gallic acid and chlorogenic acid. Gastric pH also favored the recovery of syringic and sinapic acids. Similar results were also observed in bioavailability study in in-vivo animal model with the Tmax value of both the epicatechin in peel and the catechin in rind was 2 h with a Cmax value of 62.03 and 1.10 µg/mL of plasma respectively. To conclude, the sour mangosteen fruit peel and rind polyphenols are stable in gastrointestinal tract environment and their bioactives are more bioavailable.
... garcinia fruits have been used in Indonesia for seasoning purposes, like "Asam Padeh". The principal acid of Garcinia atroviridis and Garcinia cambogia, (-)-hydroxycitric acid (HCA) has been investigated [3][4][5][6][7][8][9]. Many reports have recently shown that Garcinia atroviridis exhibit strong antimicrobial, antioxidant antitumour-promoting activities [10][11]. ...
... Earlier experimental studies have shown that Serum insulin and leptin levels in treated mice were lower than those of control mice in two groups of female Std ddY mice that were fed either a high sucrose diet or the same diet with 3.3 % Garcinia cambogia extract for 4 weeks. 32 Garcinia cambogia extract increased the release of tritiumlabeled serotonin from cultured brain cortex slices in a dosedependent manner. The maximum release of serotonin was comparable to a response elicited by K+ depolarizing stimuli. ...
Article
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Obesity and its concomitant health risks are among the most common conditions managed by health care practitioners. The limited long-term effectiveness of conventional weight management has led to researching alternative medicine and one which is widely accepted is the herbal products by virtue of its safety in long term use. The study was conducted to evaluate effect of caplet of Garcinia extract with reference to reduction in BMI and skin fold thickness in obese individuals. This study was performed according to a double-blind, randomized, placebo-controlled, design. Subjects aged 18 to 60 years with Obesity as decided by BMI > 25 Kg/m2 to 35 Kg/m2 falling in the category of overweight and class I obesity were included in the study. A total of 110 individuals participated in the study. Subjects were randomly assigned into two groups of 55 each to receive treatment for 4 months with Garcinia or matching placebo at a dose of 1 caplet twice daily. All the subjects completed the study as stipulated. At the end of 4 months, Garcinia group had significant reduction in BMI and skin fold thickness when compared to the placebo group and baseline values respectively. No severe adverse effect was observed at any time in the study period. Compliance to treatment was good. It is therefore expected that Garcinia may be useful for the prevention and reduction of obesity.
... peptide and L-carnitine by effectively lowering blood and hepatic lipid concentrations (Kim et al., 2008). Previous result showed that the serum TG and LDL-C concentrations (Hayamizu et al., 2003), these results in the present was also reduced. In the present study, curcumin-treated groups increased the liver NEFA concentration and decreased the liver TG concentration. ...
Article
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The purpose of this study was to investigate whether dietary curcumin affects lipid metabolism in the liver of broiler chickens. Four treatment groups were formed from 1200 1-day-old broiler chickens, including a base diet (control, supplemented with 0 mg/kg curcumin), 500 mg/kg, 1,000 mg/kg, and 2,000 mg/kg dietary curcumin, for 49 d. At the end of experiment, each group of 50 chickens were sampled and analyzed. Compared with the control group, the results have showed that body weight, average daily weight gain, absolute and relative liver weight significantly decreased in the 1,000 and 2,000 mg/kg curcumin groups (P < 0.05). The absolute and relative abdominal fat weight were significantly decreased in the 2,000 mg/kg curcumin group (P < 0.05). The concentrations of plasma low-density lipoprotein cholesterol (P < 0.05) and plasma and hepatic triglyceride concentrations (P < 0.01) were markedly decreased in the 2,000 mg/kg curcumin group. The hepatic nonesterified fatty acid concentration (P < 0.05) and the hepatic glycogen (P < 0.05) and liver hepatic lipase activities (P < 0.01) were significantly increased in the 1,000 and 2,000 mg/kg curcumin groups. The plasma-free triiodothyronine and thyroxine concentrations were significantly increased in the 2,000 mg/kg curcumin group (P < 0.05). The gene expression levels of fatty acid synthase (FAS) and sterol regulatory element binding protein-1c (SREBP-1c) were significantly decreased in all curcumin groups (P < 0.05), but the gene expression levels of acetyl CoA carboxylase (ACC) and ATP-citrate lyase (ACLY) were significantly decreased only in the 2,000 mg/kg curcumin group (P < 0.05). The expression levels of peroxisome proliferators-activated receptor α (PPARα) and carnitine palmitoyl transferase-I (CPT-I) were significantly increased in the 1,000 and 2,000 mg/kg curcumin groups (P < 0.05). These results indicated that curcumin plays an important role in reduction abdominal fat deposition by decreasing the hepatic and plasma lipid profile and affecting the expression levels of genes related to lipogenesis and lipolysis including ACC, FAS, SREBP-1c, ACLY, PPARα, and CPT-I.
... В связи с этим среди препаратов растительного происхождения особый интерес представляет экстракт гарцинии камбоджийской. В состав плодов гарцинии камбоджийской в качестве основных составляющих входят различные органические кислоты [21], бензофеноны и ксантоны [20]; многочисленные исследования показали, что она может предупреждать ожирение [18], обладает гиполипидемической [13], антидиабетической, противовоспалительной, антиоксидантной [29] активностью. Ее плоды содержат до 65% гидроксилимонной кислоты, пектин, полифенольные соединения различных классов, бензофеноны, ксантоцимол и изоксантоцимол, камбогин, камбогинол, гарцинол, смолистые вещества. ...
Article
BACKGROUND The species of Garcinia (Clusiaceae) are traditionally used as flavouring agents in curries and to cure several human health complications. This study investigated the contents of thirty‐one macro, micro, and trace elements in microwave assisted digested samples of Garcinia cambogia fruit and its anti‐obesity commercial products by inductively coupled plasma‐optical emission spectroscopy (ICP‐OES) and ICP‐mass spectrometric (ICP‐MS) techniques. The methods were also validated using the parameters of coefficient of determinations (R²), limits of detection and quantification (LOD, LOQ), precision (CV%), analysis of certified reference materials, spiking recovery experiments, and participation in accredited laboratory proficiency test organized by Food Analysis Performance Assessment Scheme (FAPAS). RESULTS In quality assurance, the values of applied parameters confirmed that the methods are well efficient and in accordance to the criteria set by the Association of Official Analytical Chemists (AOAC). In elemental analysis, the analyzed macro, micro and trace essential elements were present in appreciable concentrations, which can meet the human nutritional requirements. Furthermore, the contents of analyzed trace toxic elements were within the safe limits. CONCLUSION From the results of the current study, the analyzed fruit and its commercial products could be considered potential sources of mineral elements without posing any threats to consumers. This article is protected by copyright. All rights reserved.
Article
The incidence rate is directly proportional to the incidence of obesity or overweight and Type 2 diabetes mellitus. Garcinia is a plant that has been proven empirically, preclinically, and clinically to have activities for the avoidance and treatment of metabolic syndrome and on the pathogenesis and pathophysiology caused by the disease. The aim of this study is to create a discussion and summarize information regarding the activity or usefulness of the Garcinia plant. This review article was based on the published journals obtained from Google Scholar, Scopus, and PubMed databases using the keywords Garcinia obesity, Garcinia overweight, and Garcinia metabolic syndrome. Garcinia had many activities related to metabolic syndrome because it was able to reduce body fat mass, blood sugar level, body weight, total cholesterol, and triglyceride level. These activities were mediated by numerous apparatuses of feat together with a reserve of fatty acid synthase, α-amylase, α-glucosidase, and several other enzymes and pathways associated with the metabolic syndrome. Garcinia plant was able to be used as a candidate for a new herbal that had a good effect in treating metabolic syndrome in future.
Thesis
Le récepteur hépatique aux lipoprotéines LSR est impliqué dans la clairance des lipoprotéines riches en triglycérides telles que les résidus de chylomicrons pendant la phase postprandiale. La réduction de l'expression du LSR chez la souris (LSR+/-) est associée à une dyslipidémie et une lipémie postprandiale élevée. Afin de mieux comprendre la régulation de la distribution des lipides alimentaires, nous avons cherché quels étaient les facteurs pouvant affecter le niveau protéique de LSR. La leptine, hormone sécrétée par le tissu adipeux et connue pour son action d'hormone de satiété au niveau du système nerveux central, a été démontrée dans cette thèse comme modulant l'expression de LSR par la régulation de la transcription du gène lsr. La leptine est impliquée dans la régulation de la lipogénèse à travers SREBP-1. Grâce à l'utilisation d'un extrait de Garcinia cambogia contenant un inhibiteur de l'ATP citrate lyase, nous avons démontré une interaction importante entre les enzymes lipogéniques, l'expression de LSR et d'autres récepteurs lipoprotéiques, afin de maintenir un équilibre entre la synthèse de lipides endogènes et l'apport alimentaire de lipides exogènes. Soumises à un régime hyperlipidique, les souris sauvages montrent une diminution de l'expression des enzymes lipogéniques hépatiques, aggravée chez les souris LSR+/-. Ces résultats indiquent qu'il existe un mécanisme de maintien de l'équilibre entre la lipogénèse (synthèse endogène de lipides), la lipolyse (utilisation lipidique comme substrat énergétique) et le stockage de lipides à travers une forte interaction entre les enzymes lipogéniques et LSR.
Article
Being overweight and obesity are serious public health problems in numerous countries. This study describes an 8-week clinical evaluation of the effects of Garcinia cambogia and Phaseolus vulgaris extracts on overweight adults in Taiwan. In this study, 114 overweight adults were recruited and randomly divided into three groups: a G. cambogia extract group (which was given Super CitriMax) , a P. vulgaris extract group (which was given Phase 2) , and a placebo group (which was given maltodextrin) . Each participant was administered 2800 mg/day of G. cambogia extract, P. vulgaris extract, or a placebo for 8 consecutive weeks; participants' diets were not restricted during the intervention. Participants received nutritional education and anthropometric measurements once every 2 weeks starting from week 0, and hemobiochemical tests of the blood were conducted at weeks 0 and 8. The statistics of anthropometric measurements indicated that compared to week 0, by week 8 the waist, hip, and thigh circumferences of participants in the placebo group had significantly increased; whereas participants in the G. cambogia extract group had maintained their waist and hip circumferences and waist-hip ratios, while participants in the P. vulgaris extract group had also maintained their hip circumferences and waist-hip ratios. Results of the hemobiochemical analysis after 8 weeks showed that aspartate aminotransferase had decreased and fasting blood-glucose had stabilized in participants of the G. cambogia extract group, whereas high-density lipoprotein-cholesterol was elevated in participants in the P. vulgaris extract group.
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Garcinia cambogia, with its active component hydroxycitric acid (HCA), is widely used for weight loss due to its anorexigenic effect, increased fat oxidation, and regulation of endogenous lipid biosynthesis. The potential effectiveness of G. cambogia in reducing body weight and fat has been concluded in several studies in both experimental animals and humans. However, the results of some randomized placebo-controlled human clinical trials have either not reported the same outcome or there has been a marginal reduction in body weight on a short-term basis, not beyond 12 weeks. Other beneficial effects of Garcinia in experimental studies include antiinflammatory, antiulcerogenic, antioxidant, hepatoprotective, cytotoxic, erythropoietic, and miscellaneous other effects. Studies with G. cambogia conducted in experimental animals have not reported mortality or significant toxicity. Further, at doses usually recommended for humans no side effects have been reported. However, G. cambogia should not be concurrently used with other drugs to circumvent drug interactions. Currently, a large number of G. cambogia/HCA-containing dietary supplements are being marketed, although the reports of toxicity associated with the regular use of these supplements have raised concerns. In most cases complaints have been related to formulations containing multiple ingredients including G. cambogia. Another reason for adverse effects of G. cambogia/HCA can be related to idiosyncratic reactions by individual patients or other drugs used concurrently with these supplements resulting into in a drug/herb-induced toxic interaction.
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RESUMO: Este trabalho teve por objetivo avaliar os efeitos da administração de Garcinia cambogia sobre o ganho de peso e os níveis sanguíneos de glicose, triglicérides, colesterol total e suas principais frações (HDL, LDL e VLDL), ácido úrico e albumina em ratos sadios, sob dieta balanceada comercial. Para tanto, ratos Wistar, machos, pesando aproximadamente 180 gramas, foram tratados com 1 grama/kg/dia ou 2 gramas/kg/dia de extrato comercial (tintura) de Garcinia cambogia diluído na água de bebida, recebendo ração comercial ad libitum. Os animais foram pesados no início e no final do experimento. Após 20 dias ou 40 dias os animais foram anestesiados por inalação de éter etílico e submetidos à punção cardíaca para obtenção de sangue. Após coagulação e centrifugação, as amostras de soro foram analisadas utilizando-se kits comerciais para determinação bioquímica de triglicérides, colesterol total, HDL, LDL, VLDL, glicose, ácido úrico e albumina, seguindo as recomendações dos fabricantes. Os resultados foram analisados estatisticamente para comparação entre os diferentes grupos. A análise estatística revelou aumento significativo (p<0,05) dos níveis de colesterol total nos animais tratados com 2 mg/kg/dia durante 20 dias, com relação ao grupo não-tratado e tratado com 1 mg/kg/dia. Os animais tratados com Garcinia cambogia apresentaram, após 20 dias de tratamento, independente da dose, menor ganho de peso em relação aqueles não tratados. Os demais parâmetros não apresentaram variações estatisticamente significativas. Os resultados obtidos permitem concluir que, em ratos sadios sob alimentação balanceada, o tratamento durante 20 dias com 1 ou 2 g/kg de peso/dia de extrato de Garcinia cambogia induz redução significativa do ganho de peso, com aumento transitório dos níveis de colesterol total, sem alterar de forma significativa concentração plasmática de triglicérides, HDL, LDL, VLDL, ácido úrico e albumina. Palavras-chave: Garcinia cambogia, HCA, ganho de peso, bioquímica do sangue ABSTRACT: The effect of the administration of Garcinia cambogia on blood biochemical variables and body weight gain in healthy mice. The purposes of this study are to evaluate the effect of the administration of Garcinia cambogia on body weight gain and blood levels of glucose, triglycerides, the total cholesterol and its main fractions (HDL, LDL and VLDL), uric acid and albumin in healthy mice put on a commercially balanced diet. Therefore male Wistar mice, weighing approximately 180g, were treated with 1mg/kg/day or 2mg/kg/day of a standard extract of Garcinia cambogia diluted in drinking water and they had rodent processed food ad libitum. The animals were weighed at the beginning and at the end of the experiment. After 20 or 40 days, the animals were anesthetized inhaling ethylic ether and were subjected to cardiac puncture to obtain the blood. After coagulation and centrifugation, the serum samples were analysed using standard kits for the biochemical determination of triglycerides, the total cholesterol, HDL, LDL, VLDL, glucose, uric acid and albumin according to the manufacturers’ recommendations. In order to compare the different groups, the results were analysed statistically. The statistical analysis showed a considerable increase (p<0.05) of the levels of total cholesterol in the treated animals after 20 days using 2mg/kg/day, in relation to the non-treated and treated ones using 1mg/kg/day. The treated animals, which used Garcinia cambogia by 20 days, independent of dose, showed less weight gain in relation to the non-treated ones. The other parameters have not shown relevant statistical variations. The results enable us to conclude that in healthy mice who have a balanced diet, the treatment using 1 or 2 gr/kg daily of Garcinia cambogia extract induces, after 20 days, a reduction of weight gain having a transitory increase of the levels of total cholesterol, not altering the plasmatic concentration of triglycerides, HDL, LDL, VLDL, uric acid and albumin.
Article
Anti-obesity effects of β-cyclodextrin in obese C57BL/6J mice induced by a high fat diet (HD) were observed. The administration of β-cyclodextrin reduced the gain of body weight, abdominal fat, liver weight, the lipid deposits of hepatocytes and the size of adipocytes in the HD group. In serum analysis, the total and low-density lipoprotein-cholesterols were significantly decreased in the β-cyclodextrin-supplemented HD group than in the HD group. However, high-density lipoprotein-cholesterol was not changed in these groups. In hypothalamic homogenates, the decrease of neuropeptide Y and increase of α-melanocyte stimulating hormone were detected in the β-cyclodextrin- supplemented HD group compared to that in the HD group. These effects of β-cyclodextrin were similar to those of Garcinia cambogia, which is widely used as a natural anti-obesity product. These results suggest that β-cyclodextrin has anti-obesity effects through the lowering of the abdominal fat pad and inhibits the central effects of hunger.
Chapter
Obesity has become a worldwide epidemic and a major challenge to health professionals. In fact, a new term, globesity, has been coined to describe the recent upsurge of overweight and obesity in the global population. Today, obesity rates in the United States have reached epidemic proportions - 58 million Americans are overweight with a body mass index (BMI) of 25 or greater, 40 million are obese, and 3 million are morbidly obese (BMI ≥ 30); 8 out of 10 U.S. adults over 25 years of age are overweight [1,2]. These changes in rates of overweight and obesity are primarily attributed to overeating and a sedentary lifestyle. A recent survey found that 25% of Americans lead sedentary lifestyles, while 78% of Americans do not meet basic activity level recommendations. A 76% increase in type 2 diabetes in adults 30 to 40 years old has occurred since 1990 [1,2]. According to the World Health Organization (WHO), more than 1 billion adults are overweight and at least 300 millions are clinically obese worldwide. The International Obesity Task Force estimated that 22 million of the world’s children under 5 are overweight or obese [1,2]. Obesity has been shown to be associated with a broad spectrum of degenerative diseases, including metabolic disorders and certain forms of cancer. It has been reported that 80% of the cases of type 2 diabetes, 70% of cardiovascular diseases, and certain forms of cancer such as breast and colon (42%) are related to obesity [1,2]. Also, obesity is the major cause of 30% of gallbladder surgery, and 26% of obese people have high blood pressure. Among children diagnosed with type 2 diabetes, 85% are obese [2].
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Garcinia cambogia extract (GCE)/(−) – hydroxycitric acid (HCA) has been identified as a potential antiobesity agent. However, controversial clinical trial results have been published on its biological effect and poor pharmacokinetic (PK) information increases its dubious efficacy. The aim of this study was to determine the main PK parameters of GCE/HCA in healthy women, and to evaluate food effects on HCA absorption. Healthy women ages 21–41 years with body mass index (BMI; kg/m²) 20.29–25.82 participated in a phase I, open-label, randomized, single-dose, cross-over study. In the fasted- and fed-conditions subjects received 1500/750 mg of GCE/HCA under 8 h of fasting. In the fed-period was given a high calorie breakfast (~600 calories) after dosing. Plasma HCA concentrations were substantially reduced in fed-state. Peak plasma concentration (Cmax) and area under the curve of time-concentration (AUC0–10h) were 3-fold and 2-fold lower (p < 0.001, 0.01) in fed-condition, respectively. Higher volume of distribution (Vd/F) and clearance (Cl/F) were achieved in fed state, probably due to the lower fraction (F) of HCA absorbed induced by food effect. Large inter-individual variations were observed for the main pharmacokinetics parameters in both periods. These findings suggest that HCA might suffer an active absorption uptake and intense adsorption on food.
Thesis
L’obésité et le surpoids sont devenus un réel problème de santé publique dans le monde et en France. La prévention de l’obésité et la promotion d’une alimentation saine et équilibrée est la priorité des organismes de santé. Face à la multiplicité des régimes amaigrissants, à leurs pratiques hasardeuses et au choix des compléments alimentaires disponibles en officine qui peuvent y être associés, le pharmacien a pour rôle de mettre en garde le patient sur les risques de certaines pratiques. Sa mission est aussi de transmettre les notions de mesures hygiéno-diététiques afin d'orienter le patient de manière plus sécuritaire pour s’assurer de sa santé et de son bien-être.
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(-)-Hydroxycitric acid (HCA), a major active ingredient of Garcinia Cambogia extracts, had shown to suppress body weight gain and fat accumulation in animals and humans. While, the underlying mechanism of (-)-HCA has not fully understood. Thus, this study was aimed to investigate the effects of long-term supplement with (-)-HCA on body weight gain and variances of amino acid content in rats. Results showed that (-)-HCA treatment reduced body weight gain and increased feed conversion ratio in rats. The content of hepatic glycogen, muscle glycogen, and serum T4 , T3 , insulin, and Leptin were increased in (-)-HCA treatment groups. Protein content in liver and muscle were significantly increased in (-)-HCA treatment groups. Amino acid profile analysis indicated that most of amino acid contents in serum and liver, especially aromatic amino acid and branched amino acid, were higher in (-)-HCA treatment groups. However, most of the amino acid contents in muscle, especially aromatic amino acid and branched amino acid, were reduced in (-)-HCA treatment groups. These results indicated that (-)-HCA treatment could reduce body weight gain through promoting energy expenditure via regulation of thyroid hormone levels. In addition, (-)-HCA treatment could promote protein synthesis by altering the metabolic directions of amino acids.
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The present work evaluated the protective effects of Spirulina against the bone fragility caused by Garcinia cambogia in high-fat diet induced obese rats. High-fat diet and high-fat emulsion (HFD+HFE) were administered via oral gavage to 30 six-week-old female Sprague Dawley rats for six weeks to induce obesity, except for a normal group (n = 6). Following four weeks of treatment, the diet-induced obese groups were orally administered, daily, with (1) G. cambogia (GC); (2) Spirulina (S); and (3) G. cambogia + Spirulina (GC+S). The normal and obese control groups were treated with equal volumes of 0.9% saline water. It was found that GC significantly decreased body mass index (BMI) below the obese range (0.68 g/cm2). Additionally, GC altered bone mineral density (BMD), increased phosphate and calcium levels, and decreased maximum force and mineral apposition rates (MAR) as compared to the obese control group (p < 0.05). Bone fragility caused by GC was confirmed by the decrease in bone formation marker osteocalcin (OCN), as well as an increase in bone resorption receptor activator of nuclear factor kappa-B ligand (RANKL) and tartrate-resistant acid phosphatase type 5b (TRAP5b) as compared to the obese control group. Spirulina also decreased the BMI of the obese rats. Spirulina also increased blood bone markers, BMD, maximum force, and Young’s modulus. Rats supplemented with GC+S demonstrated higher double-labelled surface (dLS/BS) and MAR as compared to those in the GC group (p < 0.05). Meanwhile, the S group demonstrated improvement in all dynamic histomorphometric indices. S and GC+S groups demonstrated bone formation upregulation and bone resorption downregulation, thus indicating a bone protective effect of Spirulina. Overall, GC treatment led to bone fragility. GC+S treatment significantly augmented bone formation and mineralisation in obese rats as compared to the GC treatment alone. Rats in the S group demonstrated effective weight reduction while showing no destructive effects on the bone.
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The modern popular ideology is that plant-based products do not have adverse effects. Hence, people are fond of using herbal products of their choice to treat their own ailments or anyone else. As majority of the population are not aware of herbal toxicity concept, the use of formulated single or combined medicinal and/or nutritional plant extracts or isolated compounds to treat chronic diseases are increasingly popular due to the widespread concerns regarding the adverse effects of pharmaceutical drugs. Awareness from the scientific community to bring society to its senses regarding the safety issue of a herbal product is rare. Garcinia gummigutta (more popularly known by the synonym Garcinia cambogia in commercial preparations), belonging to the family of Clusiaceae (alt. Guttiferae) is a popularly consumed weight-loss nutraceutical. This review aims to highlight the possible adverse effects of G. cambogia. For the said purpose, 147 articles were collected from PubMed, Web of Science and Google scholar. Literature review revealed a plethora of beneficial actions. Investigational outcomes and clinical evidences hint the possible adverse effects likely to be linked with the use of G. cambogia. However, the use of G. cambogia as an anti-obesity agent is advisable as long as the therapeutic value outweighs the adverse effect.
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A simple capillary zone electrophoresis method with direct ultraviolet detection has been developed for the analysis of naturally occurring diastereomeric 2-hydroxycitric acid lactones. Using 50 mM sodium phosphate buffer of pH 7, a baseline resolution Rs > 3.0 was observed for all organic acids selected for the present study. This method was employed for the quantitative determination of title acids present in the plant sources namely G. cambogia fruit rinds and H. sabdariffa calyx. Conversion of 2-hydroxycitric acids to their lactones on heating above plant sources is deliberated. Hydrolysis of hydroxycitric acid lactones in aqueous solution is reported for the first time. This article is protected by copyright. All rights reserved.
Chapter
Cambogia gummi-guta L., Cambogia gutta L., Cambogia gutta Lindl., Garcinia affinis Wight & Arn., Garcinia cambogia (Gaertn.) Desr. nom. illeg., Garcinia conicarpa Wight, Garcinia gummi-gutta var. conicarpa (Wight) N. P. Singh, Garcinia elliptica Wall., Garcinia papilla Wight, Garcinia quaesita Pierre, Garcinia zeylanica Roxb.
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A cell-free system, consisting of particle-free cytoplasm and mitochondria prepared from rat liver, has been used to study the transfer of acetyl groups from the intramitochondrial to the extramitochondrial space during fatty acid synthesis. ¹⁴C-Pyruvate, generated from ¹⁴C-alanine, was used to generate intramitochondrial ¹⁴C-acetyl-CoA. Fatty acid synthesis was followed by measuring the incorporation of ³H2O and ¹⁴C. Pool dilution experiments showed that the acetyl group of intramitochondrial acetyl-CoA leaves the mitochondria in the form of citrate, or of a closely related tricarboxylate. (-)-Hydroxycitrate, an inhibitor of citrate cleavage enzyme, strongly inhibits fatty acid synthesis from ¹⁴C-alanine. On the other hand, (-)-hydroxycitrate has little or no effect on respiration, phosphorylation, and citrate accumulation during the course of the experiments. n-Butylmalonate, an inhibitor of malate permease, also inhibits fatty acid synthesis. This inhibition is reversed by malate. n-Butylmalonate probably exerts its effect by preventing the activation of α-ketoglutarate and tricarboxylate permeases by malate. It is concluded that citrate is the major carrier in the transfer of acetyl groups from the mitochondrial matrix to the cytoplasm.
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The four isomers of hydroxycitrate have been tested as substrates and inhibitors for citrate synthase, citrate lyase, and ATP citrate lyase. None of the isomers served as a substrate for citrate synthase and they were moderate to weak inhibitors of this reaction. Of the four isomers, only (pncit)-(2S)-2-hydroxycitrate did not serve as a substrate for citrate lyase while (pncit)-(4S)-4-hydroxycitrate was the only isomer which did not serve as a substrate for ATP citrate lyase. No consistent pattern of reactivity or inhibitor potency was seen with the different isomeric hydroxycitrates. It is proposed that more than one mode of binding is possible between the isomers and the three different active sites.
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We investigated the effects of diet-induced obesity on glucose metabolism in two strains of mice, C57BL/6J and A/J. Twenty animals from each strain received ad libitum exposure to a high-fat high-simple-carbohydrate diet or standard Purina Rodent Chow for 6 mo. Exposure to the high-fat, high-simple-carbohydrate, low-fiber diet produced obesity in both A/J and C57BL/6J mice. Whereas obesity was associated with only moderate glucose intolerance and insulin resistance in A/J mice, obese C57BL/6J mice showed clear-cut diabetes with fasting blood glucose levels of greater than 240 mg/dl and blood insulin levels of greater than 150 microU/ml. C57BL/6J mice showed larger glycemic responses to stress and epinephrine in the lean state than AJ mice, and these responses were exaggerated by obesity. These data suggest that the C57BL/6J mouse carries a genetic predisposition to develop non-insulin-dependent (type II) diabetes. Furthermore, altered glycemic response to adrenergic stimulation may be a biologic marker for this genetic predisposition to develop type II diabetes.
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Incorporation of ³H from ³H2O was used to measure the rate of fatty acid synthesis in rat liver. (—)-Hydroxycitrate strongly inhibits fatty acid synthesis in vivo.
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The obese (ob) gene, the mutation of which results in severe hereditary obesity and diabetes in mice, has recently been isolated through positional cloning. In this study, we isolated a full-length human ob complementary DNA (cDNA) clone and examined the tissue distribution of ob gene expression in humans. The nucleotide sequences of the human ob cDNA coding region were 83% identical to those of the mouse and rat ob cDNA coding regions. Analysis of the deduced amino acid sequences revealed that the human ob protein is a 166-amino acid polypeptide with a putative signal sequence and is 84 and 83% homologous to the mouse and rat ob proteins, respectively. Northern blot analysis using the cloned human ob cDNA fragment as a probe identified a single messenger RNA (mRNA) species 4.5 kb in size found abundantly in the adipose tissues obtained from the subcutaneous, omental, retroperitoneal, perilymphatic, and mesenteric fat pads. However, no significant amount of ob mRNA was present in the brain, heart, lung, liver, stomach, pancreas, spleen, small intestine, kidney, prostate, testis, colon, or skeletal muscle. The ob mRNA level in the adipose tissue varied from region to region even in the same individual. Furthermore, in the human adipose tissue, ob gene expression occurred in mature adipocytes rather than in stromal-vascular cells. This study is the first report of the elucidation of ob gene expression in human tissues, thereby leading to better understanding of the physiological and clinical implications of the ob gene.
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Despite the fact that mutations resulting in the absence of leptin or its receptor have been associated with severe obesity and diabetes, such mutations do not appear to be responsible for most human obesity. Indeed, diet-induced obesity in animals and humans has been characterized by hyperleptinemia. This has been interpreted as evidence for leptin resistance. However, no careful longitudinal studies evaluating the role of leptin in the development of obesity exist. We report a series of studies in A/J and C57BL/6J (B/6) mice that demonstrate a direct relationship between the ability to increase plasma leptin levels in response to a high-fat diet and resistance to the subsequent development of obesity and diabetes. While leptin levels are similar in lean, low-fat-fed A/J and B/6 mice, the effects of a high-fat diet on plasma leptin differ dramatically between the two strains. After 4 weeks of high-fat feeding, leptin levels in A/J mice increased 10-fold, and this elevated level was maintained independent of weight gain throughout a 14-week feeding period. However, in B/6 mice, leptin levels remained at least twofold lower and only rose very gradually along with a significant increase in adiposity, hyperglycemia, and hyperinsulinemia. These differences in the response of leptin to diet are independent of food intake and plasma insulin levels during the 1st month of feeding. Further, we demonstrated that leptin administration did not influence the expression of the novel uncoupling protein UCP2, which also responds to dietary fat. From these results, we suggest that the response of leptin to fat feeding may be an important predictor of the development of subsequent obesity.
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Obesity-resistant (A/J) and obesity-prone (C57BL/6J) mice were weaned onto low-fat (LF) or high-fat (HF) diets and studied after 2, 10, and 16 wk. Despite consuming the same amount of food, A/J mice on the HF diet deposited less carcass lipid and gained less weight than C57BL/6J mice over the course of the study. Leptin mRNA was increased in white adipose tissue (WAT) in both strains on the HF diet but to significantly higher levels in A/J compared with C57BL/6J mice. Uncoupling protein 1 (UCP1) and UCP2 mRNA were induced by the HF diet in brown adipose tissue (BAT) and WAT of A/J mice, respectively, but not in C57BL/6J mice. UCP1 mRNA was also significantly higher in retroperitoneal WAT of A/J compared with C57BL/6J mice. The ability of A/J mice to resist diet-induced obesity is associated with a strain-specific increase in leptin, UCP1, and UCP2 expression in adipose tissue. The findings indicate that the HF diet does not compromise leptin-dependent regulation of adipocyte gene expression in A/J mice and suggest that maintenance of leptin responsiveness confers resistance to diet-induced obesity.
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The principal acid in the highly acidic fruits of Garcinia cambogia has been identified as (−)-hydroxycitric acid. This acid has not been encountered in nature before. Fruits of two other species of Garcinia were found to contain the same acid, and the leaves of Hibiscus cannabinus, (+)-allo-hydroxycitric acid, an isomer reported earlier in Hibiscus sabdariffa. Wide occurrence of hydroxycitric acid in nature is thus indicated.
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These studies were designed to determine whether genetically and experimentally induced hypertriglyceridemia were correlated with hyperlipogenesis, and whether inhibiting fatty acid synthesis would reduce serum triglyceride levels. Hypertrigylceridemia, resulting from genetic obesity in Zucker rats and fructose feeding or Triton administration to Charles River rats, was examined in relation to in vivo rates of heatic fatty acid synthesis, and the influence of (--)-hydroxycitrate (a potent competitive inhibitor of ATP citrate lyase) on serum triglyceride levels and lipogenesis was determined. Zucker obese rats demonstrated significantly increased rates of fatty acid synthesis and levels of serum triglycerides compared to their lean litter mates; lipogenic rates and circulating triglycerides were reduced markedly by the oral administration of (--)-hydroxycitrate. Fructose administered in the diet or drinking water induced a hypertriglyceridemia which was associated with a marked increase in hepatic lipogenesis, and (--)-hydroxycitrate reduced significantly both parameters. In contrast to the significant role that increased rates of lipogenesis apparently played in the development of hypertriglyceridemia in the Zucker rat and fructose-fed rat, Triton given intravenously produced a marked rise in serum triglycerides which could not be accounted for, to an appreciate extent, by increased rates of fatty acid synthesis. (--)-Hydroxycitrate reduced serum triglyceride levels and hepatic lipogenic rates equivalently in the Triton-treated and nontreated rats.
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The ability of insulin to stimulate glucose uptake can vary substantially in non-obese individuals with no apparent disease (10). In addition, differences in either degree of obesity or level of habitual physical activity can also modulate in vivo insulin action (18,24). In an apparent attempt to maintain glucose homeostasis, the compensatory response to a decrease in insulin-stimulated glucose up take is an increase in plasma insulin concentration. A defect in the ability of insulin-stimulated glucose uptake has also been demonstrated (21) in patients with either impaired glucose tolerance (IGT) or non-insulin dependent diabetes mellitus (NIDDM). It has been suggested that the degree to which glucose tolerance deteriorates in these individuals is a function of the level of compensatory hyperinsulinemia that they can maintain, and the appearance of severe fasting hyperglycemia marks the failure of the pancreatic beta cell to sustain the necessary increase in insulin secretory response (21).
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These studies were designed to determine the effect of (−)-hydroxycitrate upon the accumulation of lipid in the rat by examining appetite, wt gain, and total body lipid profiles. The chronic oral administration of a nontoxic dose of (−)-hydroxycitrate to growing rats for 11–30 days caused a significant reduction in body wt gain, food consumption, and total body lipid. The administration of equimolar amounts of citrate did not alter wt gain, appetite, or body lipid. No increase in liver size or liver lipid content occurred with either treatment. Pair feeding studies demonstrated that the reduction in food intake accounted for the decrease in wt gain and body lipid observed with (−)-hydroxycitrate treatment.
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Citrate cleavage enzyme shows atypical kinetics at low chloride concentrations, but normal kinetics at high chloride concentrations. Tricarballylate is a substrate for citrate cleavage enzyme. The reaction with tricarballylate can be demonstrated both by the disappearance of CoA and, in the presence of hydroxylamine, by the appearance of a hydroxamate. This indicates that tricarballylyl-CoA is formed in the reaction. When hydroxamate formation is used to assay activity, the apparent Km for tricarballylate is about three times greater than that for citrate, while the maximum reaction velocity with tricarballylate is about 90% of that observed with citrate. One of the stereoisomers of hydroxycitrate is a powerful inhibitor of citrate cleavage enzyme.
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The relationship of clinical diabetes to body fat distribution and obesity level was examined in 15,532 women. After adjusting for relative weight, all upper body segment girth measurements (neck, bust, and waist) had strong positive associations with diabetes. In contrast, the lower body segment girth measurement (hips) had an equally strong but inverse association with diabetes. Based upon waist-to-hip girth ratio, women were divided into four subgroups. The prevalence of diabetes increased with increasing values of this ratio. Women in the upper quartile had about three times the prevalence of diabetes as women of comparable obesity level in the lowest quartile. Women with both upper body fat predominance and severe obesity had a relative risk of diabetes 10.3 times as great as nonobese subjects with lower body fat predominance. The results suggest that localization of fat in the upper body segment and severe obesity are two distinct additive risks for diabetes.
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Young Zucker lean (Fa/-) and obese (fa/fa) female rats were fed the fatty acid synthesis inhibitor (-)-hydroxy-citrate as a dietary admixture for 39 days. In the lean rats, (-)-hydroxycitrate treatment decreased body weight, food intake, percent of body fat, and fat cell size. In the obese rat, food intake and body weight were reduced but the percent of body fat remained unchanged. Throughout the treatment period, obese rats maintained a fat cell size equivalent to their obese controls. Although a reduction in fat cell number in the obese rats occurred during the treatment period, marked hyperplasia was observed during the posttreatment period. The results of this study indicate that the obese rat, despite a substantial reduction in body weight produced by (-)-hydroxycitrate, still defends its obese body composition.
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Epidemiologic and clinical studies have shown a close association between hypertension, hyperlipidemia and glucose intolerance. A metabolic imbalance has been proposed. As both hyperinsulinemia and insulin resistance appear to be of pathogenetic importance in this metabolic syndrome, we studied these features in hypertensive and normotensive subjects. Glucose disposal under a hyperinsulinemic clamp was measured and different indices of hyperinsulinemia were obtained with the intravenous glucose tolerance test. The results were evaluated in relation to different cardiovascular risk factors assessed in 194 adult subjects selected from a health screening. Both hyperinsulinemia and the glucose disposal (clamped) value were significantly correlated with blood pressure (r = 0.36 and -0.42, respectively; both P < 0.0001), free fatty acids (r = 0.20 and -0.29, respectively; both P < 0.0005), serum triglycerides (r = 0.33 and -0.39, respectively; both P < 0.0001), high-density lipoprotein (HDL) cholesterol (r = -0.31 and 0.41, respectively; both P < 0.001) and fasting glucose (r = 0.45 and -0.44, respectively; both P < 0.0001). Multiple regression analysis with age, sex and obesity as confounding variables showed that insulin resistance was superior to hyperinsulinemia in the relationships with blood pressure and indices of hyperlipidemia (elevated free fatty acids, serum triglycerides and low HDL cholesterol), but both insulin sensitivity and hyperinsulinemia were significantly related to fasting glucose. Insulin sensitivity was more closely related to blood pressure, serum triglycerides and HDL cholesterol than hyperinsulinemia, but both insulin sensitivity and the insulin levels were associated with fasting glucose. Thus, insulin resistance is more important than hyperinsulinemia as a determinant of the constellation of cardiovascular risk factors comprising hypertension, glucose intolerance and hyperlipidemia.
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Although the disorders associated with obesity have been extensively studied, little attention has been paid to the fact that obesity is itself a chronic disease. This misunderstanding of the nature of obesity has contributed to the stigmatization of obese persons and to the use of inappropriate or inadequate treatment regimens. Although the etiology of obesity is still unclear, genetic, metabolic, and social factors are all believed to play a role in its development and progression. Behavioral therapy, exercise, very-low-calorie diets, drug therapy, and surgery affect the treatment of obesity of differing levels of severity. The regaining of weight following treatments other than surgery is very frequent, in part because periods of weight loss are rarely followed by maintenance programs. An increasing awareness of the chronic, multifactorial nature of obesity will ideally lead to the development of new long-term treatment programs that are safe and effective. Such programs are urgently needed in light of new data that show that the prevalence of obesity is increasing in the United States, as much as 30% in the last decade.
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Leptin, the OB gene product, is an adipocyte-derived circulating protein. In several rodent models of obesity, such as the db/db mice, fa/fa rats, and ventromedial hypothalamus-lesioned mice, as well as adult obese subjects, leptin mRNA expression and the circulating levels are elevated, suggesting resistance to its action. However, it is unknown whether the rise in leptin concentration occurs early in the natural evolution of human obesity or is a chronic adaptation to the obese state. Moreover, whether the distribution of body fat (i.e., visceral vs. subcutaneous abdominal fat) influences circulating leptin levels has not been assessed. We have determined in a group of obese and nonobese children and young adults whether leptin levels 1) are increased early in the development of obesity, 2) are related to a specific fat depot measured by magnetic resonance imaging, 3) vary during hyperinsulinemic, euglycemic, and hyperglycemic clamp studies, and 4) are different in males vs. females. In the basal state, leptin levels were elevated in obese children. Children and adults demonstrated a strong positive correlation between leptin concentrations and the subcutaneous fat depot (r = 0.84, P < 0.001). Surprisingly, a weaker correlation was found with visceral fat mass (r = 0.59, P = 0.001). Leptin levels remained unchanged under both euglycemic and hyperglycemic hyperinsulinemic conditions in both obese and nonobese subjects. A pronounced effect of gender on leptin levels was also observed. We conclude that, early in the development of juvenile obesity, leptin concentrations are elevated and are more closely linked to subcutaneous than visceral fat mass. Acute increases in insulin concentrations do not affect circulating leptin levels.
Article
It has previously been demonstrated that plasma leptin correlates to body fat content. Increased body fat content is accompanied by low insulin sensitivity, which is compensated with increased insulin secretion. We therefore studied whether plasma levels of leptin also correlate to insulin secretion and sensitivity in humans. Therefore, we examined insulin sensitivity by the euglycemic-hyperinsulinemic clamp technique and measured the insulin response to intravenous arginine (5 g) at fasting and 14 mmol/l glucose in postmenopausal women. Percent body fat content was determined with impedance measurements. Log plasma leptin significantly correlated to percent body fat (r = 0.84, P < 0.001). In women with normal glucose tolerance (n = 36), partial correlation studies controlling for body fat content revealed significant correlations between log plasma leptin and fasting insulin levels (r = 0.39, P = 0.029), the insulin response to arginine at both glucose levels (r = 0.38 and r = 0.37, P < 0.036 for both), and the glucose potentiation of arginine-stimulated insulin secretion (r = 0.40, P = 0.025). In contrast, in women with impaired glucose tolerance (n = 17), these correlations were not significant. Plasma leptin did not correlate with insulin sensitivity independently of body fat content. To study whether the correlation between leptin and insulin would be explained by insulin stimulating leptin secretion, we examined plasma leptin during hyperinsulinemic conditions (689 +/- 41 pmol/l), under both euglycemia (5.0 mmol/l, n = 10) and hypoglycemia (2.5 mmol/l, n = 7). However, under both these conditions, plasma leptin was unaltered. In conclusion, plasma leptin 1) reflects body fat content and 2) correlates to insulin secretion independently of percent body fat in postmenopausal women with normal glucose tolerance.
Article
Leptin mediates its effects on food intake through the hypothalamic form of its receptor OB-R. Variants of OB-R are found in other tissues, but their function is unknown. Here, an OB-R variant was found in human hepatic cells. Exposure of these cells to leptin, at concentrations comparable with those present in obese individuals, caused attenuation of several insulin-induced activities, including tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1), association of the adapter molecule growth factor receptor-bound protein 2 with IRS-1, and down-regulation of gluconeogenesis. In contrast, leptin increased the activity of IRS-1-associated phosphatidylinositol 3-kinase. These in vitro studies raise the possibility that leptin modulates insulin activities in obese individuals.
Article
Leptin, the product of the human homologue of the ob gene, which is defective in the obese (ob/ob) mouse, may be a humoral regulator of human adiposity. Plasma leptin concentrations were measured by RIA in 19 normal weight [body mass index (BMI) = 24.5 +/- 0.6 kg/m2] and 19 overweight to obese (BMI = 34.7 +/- 1.2 kg/m2) nondiabetic postmenopausal women on sequential controlled weight-maintaining diets containing 31%, 23%, and 14% of energy as fat, each for 4-6 weeks. Thereafter, the subjects ate a very low fat diet (< 15%) ad libitum; plasma leptin and insulin concentrations, BMI, percent body fat (%BF), and resting energy expenditure were determined after 6 and 8 months. Absolute and adiposity-corrected plasma leptin levels were higher in overweight/obese women (37.7 +/- 3.5 ng/mL; 1.01 +/- 0.07 ng.mL-1.%BF-1) than in normal weight women (16.9 +/- 2.2 ng/mL; 0.57 +/- 0.06 ng.mL-1.%BF-1, both P < 0.005 vs. obese), but were not different between the 31%, 23%, and 14% fat diets when body weight was stable. Plasma leptin was highly correlated with BMI (r = 0.81, P < 0.0001), %BF (r = 0.80, P < 0.0001), and fasting plasma insulin (r = 0.61, P < 0.0001). After 8 months on the ad libitum low fat diet, the women had lost an average of 6.9 +/- 1.0% of body mass (-2.0 +/- 0.3 kg/m2, P < 0.0001). In 15 subjects who lost more than 7% of body mass (-12.3 +/- 1.0%), plasma leptin concentrations decreased (-9.6 +/- 1.9 ng/mL, P < 0.0005), and the decrease of plasma leptin per change of adiposity (delta leptin/delta %BF) was greater in overweight/obese women (3.6 +/- 0.5) than in normal weight women (0.9 +/- 0.4, P < 0.01 vs. obese). In 18 other subjects who lost less than 7% of body mass (-2.7 +/- 0.6%), plasma leptin was unchanged (+1.4 +/- 1.4 ng/mL). Overall, the change of plasma leptin was significantly correlated with change of BMI (r = 0.43, P < 0.02), the change of %BF (r = 0.49, P < 0.005), the change of resting energy expenditure (r = 0.40, P < 0.02), and with the change of plasma insulin independently of changes of body adiposity (r = 0.45, P < 0.01). We conclude that plasma leptin concentrations are: 1) not affected by dietary fat content per se; 2) highly correlated with BMI, %BF, and plasma insulin in both overweight/obese and normal weight women; 3) decreased in parallel with plasma insulin after sustained weight loss; and 4) decreased more in overweight/obese than in normal weight women.
Article
Obesity is a major risk factor for morbidity and mortality, and a series of pharmacologic approaches are available for helping to manage the problem. Obesity is caused by an imbalance between caloric intake and energy expenditure, which is influenced by both environmental and genetic factors. Pharmacologic treatments include anorexigenic agents, which fall into two broad categories: those that act via brain catecholamine pathways and those that act via serotonin pathways. The most recent oral agents approved are dexfenfluramine, which is currently being marketed, and sibutramine. Both agents inhibit the control reuptake of serotonin but in addition may have effects on thermogenesis. Under investigation are agents that increase energy expenditure: the beta 3-adrenergic receptor agonists and drugs that prevent the intestinal absorption of free fatty acids and cholesterol. In development are innovative approaches to influence leptin and its receptors, various obesity genes, and biologic substances thought to influence satiety (neuropeptide Y, enterostatin, cholecystokinin, bombesin, and amylin). Obesity has now become a major target for drug development not only for affecting obesity per se but also for managing and preventing comorbid conditions such as diabetes and cardiovascular disease.
Article
The classification of diabetes mellitus and the tests used for its diagnosis were brought into order by the National Diabetes Data Group of the USA and the second World Health Organization Expert Committee on Diabetes Mellitus in 1979 and 1980. Apart from minor modifications by WHO in 1985, little has been changed since that time. There is however considerable new knowledge regarding the aetiology of different forms of diabetes as well as more information on the predictive value of different blood glucose values for the complications of diabetes. A WHO Consultation has therefore taken place in parallel with a report by an American Diabetes Association Expert Committee to re-examine diagnostic criteria and classification. The present document includes the conclusions of the former and is intended for wide distribution and discussion before final proposals are submitted to WHO for approval. The main changes proposed are as follows. The diagnostic fasting plasma (blood) glucose value has been lowered to > or =7.0 mmol l(-1) (6.1 mmol l(-1)). Impaired Glucose Tolerance (IGT) is changed to allow for the new fasting level. A new category of Impaired Fasting Glycaemia (IFG) is proposed to encompass values which are above normal but below the diagnostic cut-off for diabetes (plasma > or =6.1 to <7.0 mmol l(-1); whole blood > or =5.6 to <6.1 mmol l(-1)). Gestational Diabetes Mellitus (GDM) now includes gestational impaired glucose tolerance as well as the previous GDM. The classification defines both process and stage of the disease. The processes include Type 1, autoimmune and non-autoimmune, with beta-cell destruction; Type 2 with varying degrees of insulin resistance and insulin hyposecretion; Gestational Diabetes Mellitus; and Other Types where the cause is known (e.g. MODY, endocrinopathies). It is anticipated that this group will expand as causes of Type 2 become known. Stages range from normoglycaemia to insulin required for survival. It is hoped that the new classification will allow better classification of individuals and lead to fewer therapeutic misjudgements.
Article
It has been proposed that leptin and insulin through central effects are involved in the regulation of energy balance and body weight. Whether circulating leptin or insulin levels predict subsequent changes in body weight is, however, not known. We examined plasma leptin and insulin at 2, 3, 6, 9 and 12 months of age in C57BI/6J mice given a normal diet (n = 12) or a high-fat diet (58% fat on a caloric base; n = 15). Plasma leptin levels increased by age and correlated with body weight in the entire material (r = 0.81, P < 0.001). Also plasma insulin increased by high-fat diet and correlated across all age periods with body weight (r = 0.56, P < 0.001). In mice, given normal diet, plasma leptin or insulin did not correlate to subsequent changes in body weight at any of the time points studied. However, in mice given the high-fat diet, plasma leptin at 6 (r = -0.57, P = 0.027) and 9 months of age (r = -0.56, P = 0.042) as well as plasma insulin at 6 (r = - 0.51, P = 0.049) and 9 months (r = -0.58, P = 0.037) correlated inversely to the change in body weight during the subsequent 3-month period. Hence, both leptin and insulin are negative predictors for future weight gain in high-fat fed mice. This suggests that when the regulation of body weight is challenged by a high-fat diet, leptin and insulin act to restrain or prevent future weight gain. This in turn may suggest that impairment of these (probably central) actions of leptin and insulin might underlie excessive increase in body weight under such conditions.
Article
Transcriptional regulation of ATP citrate-lyase (ACL, one of the lipogenic enzymes) gene by glucose/insulin, polyunsaturated fatty acid (PUFA), and leptin has been investigated in hepatocytes and adipocytes of obese Wistar fatty rats and their lean littermates. The sequence spanning nucleotides -64 to -41 of the ACL gene, which is responsive to glucose/insulin stimulation, was linked to a reporter gene and transfected into rat hepatocytes or adipocytes. The chloramphenicol acetyltransferase (CAT) activities in the presence of glucose alone were similar in primary cultured cells from both obese and lean rats. In the presence of glucose/insulin, however, the CAT activities were markedly increased in the hepatocytes of lean rats, but were not significantly increased in those of obese rats. The stimulation by glucose/insulin was reduced in PUFA-treated cells of lean rats. The stimulation was also reduced in leptin-treated cells or ob gene expression vector-containing cells. However, PUFA- or leptin-treated cells from obese rats did not show a significant reduction in insulin stimulation. The same effects were observed at the endogenous mRNA and enzyme levels. Similar results were seen in adipocytes, although the stimulation and suppression levels were much smaller than in hepatocytes. The expression of endogenous insulin receptor in hepatocytes and adipocytes was reduced in the presence of leptin or PUFA. We previously found that insulin-binding capacities are also reduced in the presence of leptin or PUFA and are very low in obese rats in comparison with lean. Moreover, gel mobility shift assays using end-labeled ACL-(-64/-41) revealed that nuclear factor(s) including Sp1 bind specifically to the sequence, and DNA-protein complex formation is reduced in the obese rats. Thus, the reductions in the insulin-stimulated ACL transcription may be ascribed in part to reductions in insulin binding to receptors and DNA-protein complex formation.
):129. w11x Lowenstein JM
  • M Weiser
  • Wh Frishman
  • Michaelson Md
  • Abdeen Ma
  • Rs Surwit
  • Cm Kuhn
  • C Cochrane
  • Ja Mccubbin
  • Rupley Aj
  • Jr Dc
  • Kalkhoff Rd
  • Herman D Rh Zakim
  • Gordon
  • Lewis Ys Wcg
  • Ja Watson
  • Lowenstein
  • Ja Watson
  • M Fang
  • Lowenstein
  • M Singh
  • Pa Srere
  • Glusker Jp
  • Hamilton J Jg Triscari
  • Miller
  • On
  • Ac Sullivan
  • Ac Sullivan
  • J Triscari
  • Spiegel He W14x Greenwood Mrc
  • Cleary Mp
  • R Gruen
  • D Blase
  • Js Stern
  • J Triscari
Weiser M, Frishman WH, Michaelson MD, Abdeen MA. J Clin Pharmacol 1997;37(1):453. w2x Surwit RS, Kuhn CM, Cochrane C, McCubbin JA, Feinglos MN. Diabetes 1988;37(9):1163. w3x Stunkard AJ. Am J Med 1996;100(2):230. w4x Hartz AJ, Rupley Jr DC, Kalkhoff RD, Rimn AA. Prev Med 1983;12(2):351. w5x Zakim D, Herman RH, Gordon WCG. Biochem Med 1969;2:427. w6x Lewis YS, Neelakantan S. Phytochemistry 1965;4(4):619. w7x Watson JA, Lowenstein JM. J Biol Chem 1970;245(22):5993. w8x Watson JA, Fang M, Lowenstein JM. Arch Biochem Biophys 1969;135(1):209. w9x Sullivan AC, Singh M, Srere PA, Glusker JP. J Biol Chem 1977;252(21):7583. w10x Sullivan AC, Triscari J, Hamilton JG, Miller ON. Lipids 1974;9(2):129. w11x Lowenstein JM. J Biol Chem 1971;246(3):629. w12x Sullivan AC, Triscari J. Am J Clin Nutr 1977;30(5):767. w13x Sullivan AC, Triscari J, Spiegel HE. Am J Clin Nutr 1977;30(5):777. w14x Greenwood MRC, Cleary MP, Gruen R, Blase D, Stern JS, Triscari J, et al. Am J Physiol 1981;240(1):E72. w15x Masuzaki H, Ogawa Y, Isse N. Diabetes 1995;44(7):855. w16x Ahren B. Acta Physiol Scand 1999;165(2):233. w17x Watson PM, Commins SP, Beiler RJ, Hatcher HC, Gettys TW. Am J Physiol 2000;279(2):E356. w18x Larsson H, Elmstahl S, Ahren B. Diabetes 1996;45(11):1580. w19x Harvel PJ, Kasim-Karakas S, Mueller W, Johnson PR, Gingerich RL, Stern JS. J Clin Endocrinol Metab 1996;81(12):4406. w20x Reaven GM. Diabetes 1988;37(12):1595. w21x Alberti KG, Zimmet PZ. Diabete Med 1998;15(7):539. w22x Tadokoro N, Inadera H, Ishikawa H, Murano T, Shirai A, Saito Y, Yoshida S. 12th Himangakkai kiroku (in Japanese) 1991. p. 123. w23x Fukuda H, Iritani N. J Biochem 1999;126(2):437. w24x Lind L, Lithel H, Pollare T. J Hyperten 1993;11(Suppl. 4):S11. w25x Cohen B, Novick C, Rubinstein M. Science 1996;274(5290):1185. w26x Surwit RS, Petro AE, Parekh P, Collins S. Diabetes 1997;46(9):1516. w27x Caprio S, Tamborlane WV, Silver D, Robinson C, Leibel R, McCarthy S, et al. Am J Physiol 1996;271(3.1):E626.
  • Surwit