Dataset Information

Mangiferin stimulates carbohydrate oxidation and protects against metabolic disorders induced by high-fat diets.

ABSTRACT: Excessive dietary fat intake causes systemic metabolic toxicity, manifested in weight gain, hyperglycemia, and insulin resistance. In addition, carbohydrate utilization as a fuel is substantially inhibited. Correction or reversal of these effects during high-fat diet (HFD) intake is of exceptional interest in light of widespread occurrence of diet-associated metabolic disorders in global human populations. Here we report that mangiferin (MGF), a natural compound (the predominant constituent of Mangifera indica extract from the plant that produces mango), protected against HFD-induced weight gain, increased aerobic mitochondrial capacity and thermogenesis, and improved glucose and insulin profiles. To obtain mechanistic insight into the basis for these effects, we determined that mice exposed to an HFD combined with MGF exhibited a substantial shift in respiratory quotient from fatty acid toward carbohydrate utilization. MGF treatment significantly increased glucose oxidation in muscle of HFD-fed mice without changing fatty acid oxidation. These results indicate that MGF redirects fuel utilization toward carbohydrates. In cultured C2C12 myotubes, MGF increased glucose and pyruvate oxidation and ATP production without affecting fatty acid oxidation, confirming in vivo and ex vivo effects. Furthermore, MGF inhibited anaerobic metabolism of pyruvate to lactate but enhanced pyruvate oxidation. A key target of MGF appears to be pyruvate dehydrogenase, determined to be activated by MGF in a variety of assays. These findings underscore the therapeutic potential of activation of carbohydrate utilization in correction of metabolic syndrome and highlight the potential of MGF to serve as a model compound that can elicit fuel-switching effects.

SUBMITTER: Apontes P

PROVIDER: S-EPMC4207399 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Mangiferin stimulates carbohydrate oxidation and protects against metabolic disorders induced by high-fat diets.

Apontes Pasha P Liu Zhongbo Z Su Kai K Benard Outhiriaradjou O Youn Dou Y DY Li Xisong X Li Wei W Mirza Raihan H RH Bastie Claire C CC Jelicks Linda A LA Pessin Jeffrey E JE Muzumdar Radhika H RH Sauve Anthony A AA Chi Yuling Y

Diabetes 20140521 11

Excessive dietary fat intake causes systemic metabolic toxicity, manifested in weight gain, hyperglycemia, and insulin resistance. In addition, carbohydrate utilization as a fuel is substantially inhibited. Correction or reversal of these effects during high-fat diet (HFD) intake is of exceptional interest in light of widespread occurrence of diet-associated metabolic disorders in global human populations. Here we report that mangiferin (MGF), a natural compound (the predominant constituent of M ...[more]

PMID: 24848064

Similar Datasets

Project description:Obesity is a risk factor for many chronic diseases, and is associated with increased incidence rate of type 2 diabetes, hypertension, dyslipidemia and cardiovascular diseases. Adipocyte differentiation play critical role during development of obesity. Latexin (LXN), a mammalian carboxypeptidase inhibitor, plays important role in the proliferation and differentiation of stem cells, and highlights as a differentiation-associated gene that was significantly downregulated in prostate stem cells and whose expression increases through differentiation. However, it is unclear whether LXN is involved in adipocyte differentiation. The aim of this study was to evaluate the role of LXN on adipocyte differentiation, as well as its effects on high fat-induced obesity and metabolic disorders. In this study, we determine the expression of LXN in adipose tissue of lean and fat mice by Western blot, qPCR and immunohistochemistry. We found that LXN in fat tissues was continuous increased during the development of diet-induced obesity. We fed wild-type (WT) and LXN-/-mice with high-fat diet (HFD) to study the effects of LXN on obesity and related metabolic functions. We found that mice deficient in LXN showed resistance against high-fat diet (HFD)-induced obesity, glucose tolerance, insulin tolerance and hepatic steatosis. In vitro studies indicated that LXN was highly induced during adipocyte differentiation, and positively regulated adipocyte differentiation and adipogenesis in 3T3-L1 cells and primary preadipocytes. Functional analysis revealed that the expression of LXN was positively regulated by mTOR/RXR/PPARɤ signaling pathway during the differentiation of adipocytes, while LXN deletion decreased the protein level of PPARɤ in adipocyte through enhancing FABP4 mediated ubiquitination, which led to impaired adipocyte differentiation and lipogenesis. Collectively, our data provide evidence that LXN is a key positive regulator of adipocyte differentiation, and therapeutics targeting LXN could be effective in preventing obesity and its associated disorders in clinical settings.

Project description:BackgroundLow-carbohydrate diets are popular for weight loss, but their cardiovascular effects have not been well-studied, particularly in diverse populations.ObjectiveTo examine the effects of a low-carbohydrate diet compared with a low-fat diet on body weight and cardiovascular risk factors.DesignA randomized, parallel-group trial. (ClinicalTrials.gov: NCT00609271).SettingA large academic medical center.Participants148 men and women without clinical cardiovascular disease and diabetes.InterventionA low-carbohydrate (<40 g/d) or low-fat (<30% of daily energy intake from total fat [<7% saturated fat]) diet. Both groups received dietary counseling at regular intervals throughout the trial.MeasurementsData on weight, cardiovascular risk factors, and dietary composition were collected at 0, 3, 6, and 12 months.ResultsSixty participants (82%) in the low-fat group and 59 (79%) in the low-carbohydrate group completed the intervention. At 12 months, participants on the low-carbohydrate diet had greater decreases in weight (mean difference in change, -3.5 kg [95% CI, -5.6 to -1.4 kg]; P = 0.002), fat mass (mean difference in change, -1.5% [CI, -2.6% to -0.4%]; P = 0.011), ratio of total-high-density lipoprotein (HDL) cholesterol (mean difference in change, -0.44 [CI, -0.71 to -0.16]; P = 0.002), and triglyceride level (mean difference in change, -0.16 mmol/L [-14.1 mg/dL] [CI, -0.31 to -0.01 mmol/L {-27.4 to -0.8 mg/dL}]; P = 0.038) and greater increases in HDL cholesterol level (mean difference in change, 0.18 mmol/L [7.0 mg/dL] [CI, 0.08 to 0.28 mmol/L {3.0 to 11.0 mg/dL}]; P < 0.001) than those on the low-fat diet.LimitationLack of clinical cardiovascular disease end points.ConclusionThe low-carbohydrate diet was more effective for weight loss and cardiovascular risk factor reduction than the low-fat diet. Restricting carbohydrate may be an option for persons seeking to lose weight and reduce cardiovascular risk factors.Primary funding sourceNational Institutes of Health.

Project description:Background and aimsLow-carbohydrate diets (LCD) and low-fat diets (LFD) have shown beneficial effects on the management of obesity. Epidemiological studies were conducted to compare the effects of the two diets. However, the results were not always consistent. This study aimed to conduct a meta-analysis to compare the long-term effects of LCD and LFD on metabolic risk factors and weight loss in overweight and obese adults.MethodsWe performed a systematic literature search up to 30 March, 2022 in PubMed, EMBASE, and Cochrane Library. The meta-analysis compared the effects of LCD (carbohydrate intake ≤ 40%) with LFD (fat intake < 30%) on metabolic risk factors and weight loss for ≥6 months. Subgroup analyses were performed based on participant characteristics, dietary energy intake, and the proportions of carbohydrates.Results33 studies involving a total of 3,939 participants were included. Compared with participants on LFD, participants on LCD had a greater reduction in triglycerides (-0.14 mmol/L; 95% CI, -0.18 to -0.10 mmol/L), diastolic blood pressure (-0.87 mmHg; 95% CI, -1.41 to -0.32 mmHg), weight loss (-1.33 kg; 95% CI, -1.79 to -0.87 kg), and a greater increase in high-density lipoprotein cholesterol (0.07 mmol/L; 95% CI, 0.06 to 0.09 mmol/L) in 6-23 months. However, the decrease of total cholesterol (0.14 mmol/L; 95% CI, 0.07 to 0.20 mmol/L) and low-density lipoprotein cholesterol (0.10 mmol/L; 95% CI, 0.06 to 0.14 mmol/L) was more conducive to LFD in 6-23 months. There was no difference in benefits between the two diets after 24 months. Subgroup analyses showed no significant difference in the reduction of total cholesterol, low-density lipoprotein cholesterol, and blood pressure between the two diets in participants with diabetes, hypertension, or hyperlipidemia.ConclusionThe results suggest that LCD and LFD may have specific effects on metabolic risk factors and weight loss in overweight and obese adults over 6 months. At 24 months, the effects on weight loss and improvement of metabolic risk factors were at least the same. These indicated that we might choose different diets to manage the overweight and obese subjects. However, the long-term clinical efficacy and effects of various sources of carbohydrates or fat in the two diets need to be studied in the future.

Dataset Information

Mangiferin stimulates carbohydrate oxidation and protects against metabolic disorders induced by high-fat diets.

Publications

Mangiferin stimulates carbohydrate oxidation and protects against metabolic disorders induced by high-fat diets.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets