Dietary Cocoa Flavanols Enhance Mitochondrial Function in Skeletal Muscle and Modify Whole-Body Metabolism in Healthy Mice

Mitochondrial dysfunction is widely reported in various diseases and contributes to their pathogenesis. We assessed the effect of cocoa flavanols supplementation on mitochondrial function and whole metabolism, and we explored whether the mitochondrial deacetylase sirtuin-3 (Sirt3) is involved or not. We explored the effects of 15 days of CF supplementation in wild type and Sirt3-/- mice. Whole-body metabolism was assessed by indirect calorimetry, and an oral glucose tolerance test was performed to assess glucose metabolism. Mitochondrial respiratory function was assessed in permeabilised fibres and the pyridine nucleotides content (NAD+ and NADH) were quantified. In the wild type, CF supplementation significantly modified whole-body metabolism by promoting carbohydrate use and improved glucose tolerance. CF supplementation induced a significant increase of mitochondrial mass, while significant qualitative adaptation occurred to maintain H2O2 production and cellular oxidative stress. CF supplementation induced a significant increase in NAD+ and NADH content. All the effects mentioned above were blunted in Sirt3-/- mice. Collectively, CF supplementation boosted the NAD metabolism that stimulates sirtuins metabolism and improved mitochondrial function, which likely contributed to the observed whole-body metabolism adaptation, with a greater ability to use carbohydrates, at least partially through Sirt3.

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Glucose tolerance and insulin action in healthy centenarians

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.270.5.e890 ◽

1996 ◽

Vol 270 (5) ◽

pp. E890-E894 ◽

Cited By ~ 22

Author(s):

G. Paolisso ◽

A. Gambardella ◽

S. Ammendola ◽

A. D'Amore ◽

V. Balbi ◽

...

Keyword(s):

Glucose Tolerance ◽

Plasma Glucose ◽

Insulin Action ◽

Glucose Tolerance Test ◽

Tolerance Test ◽

Fat Free Mass ◽

Whole Body ◽

Glucose Disposal ◽

Oral Glucose ◽

Aged Subjects

Advancing age has been found to be associated with a decline in insulin action. Nevertheless, no study has been conducted in healthy centenarians. Our study investigates glucose tolerance and insulin action in centenarians. Fifty-two subjects were enrolled. The subjects were divided in three groups as follows: 1) adults (< 50 yr; n = 20);2) aged subjects (> 75 yr; n = 22); and 3) centenarians (> 100 yr; n = 14). Body composition was studied by bioimpedance analysis. In all subjects, an oral glucose tolerance test and euglycemic glucose clamp were performed. Centenarians have a lower fat-free mass (FFM) than aged subjects and adults, whereas fasting plasma glucose, triglycerides, free fatty acids, urea, and creatinine were not different in the groups studies. Centenarians had a 2-h plasma glucose concentration (6.0 +/- 0.2 mmol/l) that was lower than that in aged subjects (6.6 +/- 0.5 mmol/l, P < 0.05) but not different from adults [6.4 +/- 0.4 mmol/l, P = not significant (NS)]. During the clamp, plasma glucose and insulin concentrations were similar in the three groups. In these conditions, centenarians had a whole body glucose disposal (34.1 +/- 0.6 mumol.kg FFM-1.min 1) that was greater than that in aged subjects (23.3 +/- 0.5 mumol.kg FFM-1.min-1 P < 0.01) but not different from adults (34.6 +/- 0.5 mumol/kg x min, P = NS). In conclusion, our study demonstrates that centenarians compared with aged subjects had a preserved glucose tolerance and insulin action.

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No difference in exogenous carbohydrate oxidation during exercise in children with and without impaired glucose tolerance

Journal of Applied Physiology ◽

10.1152/japplphysiol.00419.2016 ◽

2016 ◽

Vol 121 (3) ◽

pp. 724-729 ◽

Cited By ~ 3

Author(s):

Lisa Chu ◽

Katherine M. Morrison ◽

Michael C. Riddell ◽

Sandeep Raha ◽

Brian W. Timmons

Keyword(s):

Insulin Sensitivity ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Area Under The Curve ◽

Tolerance Test ◽

Normal Glucose Tolerance ◽

Whole Body ◽

Oral Glucose ◽

Insulin Resistant ◽

Glucose Levels

The capacity to match carbohydrate (CHO) utilization with availability is impaired in insulin-resistant, obese adults at rest. Understanding exogenous carbohydrate (CHOexo) oxidation during exercise and its association to insulin resistance (IR) is important, especially in children at risk for type 2 diabetes. Our objective was to examine the oxidative efficiency of CHOexo during exercise in obese children with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT). Children attended two visits and were identified as NGT ( n = 22) or IGT ( n = 12) based on 2-h oral glucose tolerance test (OGTT) glucose levels of <7.8 mmol/l or ≥7.8 mmol/l, respectively. Anthropometry, body composition, and aerobic fitness (V̇o2max) were assessed. Insulin and glucose at baseline, 30, 60, 90, and 120 min during the OGTT were used to calculate measures of insulin sensitivity. On a separate day, a 13C-enriched CHO drink was ingested before exercise (3 × 20 min bouts) at 45% V̇o2max. Breath measurements were collected to calculate CHOexo oxidative efficiency. CHOexo oxidative efficiency during exercise was similar in IGT (17.0 ± 3.6%) compared with NGT (17.1 ± 4.4%) ( P = 0.90) despite lower whole body insulin sensitivity in IGT at rest ( P = 0.02). Area under the curve for insulin (AUCins) measured at rest during the OGTT was greater in IGT compared with NGT ( P = 0.04). The ability of skeletal muscle to utilize CHOexo was not impaired during exercise in children with IGT.

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Insulin dynamics and biochemical markers for predicting impaired glucose tolerance in obese Thai youth

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2014-0273 ◽

2015 ◽

Vol 28 (9-10) ◽

Author(s):

Sirapassorn Tirabanchasak ◽

Sukumarn Siripunthana ◽

Vichit Supornsilchai ◽

Suttipong Wacharasindhu ◽

Taninee Sahakitrungruang

Keyword(s):

Insulin Sensitivity ◽

Glucose Tolerance ◽

Impaired Glucose Tolerance ◽

Cell Function ◽

Density Lipoprotein ◽

Tolerance Test ◽

Normal Glucose Tolerance ◽

Whole Body ◽

Oral Glucose ◽

Sensitivity Indices

AbstractSubjects with impaired glucose tolerance (IGT) are at risk for type 2 diabetes mellitus (T2DM) and cardiovascular disease. The predictors of IGT in obese youth are not well described.We studied 115 obese Thai children who underwent an oral glucose tolerance test (OGTT). Plasma glucose and insulin levels were calculated for assessment of β-cell function. Hemoglobin A1c (HbA1c), lipid profile, and clinical parameters were also used to determine predictors of IGT.We found that three patients had T2DM and 30 subjects had IGT. IGT patients had significantly higher fasting glucose (FG), 1-h postload glucose, 2-h postload insulin, and lower whole-body insulin sensitivity indices than in normal glucose tolerance subjects whereas other indices were comparable. By ROC curve analyses, 1-h postload glucose was the best predictor of IGT, but FG or HbA1c represented a poor diagnostic tool for prediabetes screening. Subjects with 1-h OGTT glucose >155 mg/dL had significantly lower high-density lipoprotein levels, lower insulin sensitivity, and more insulin resistance than those with 1-h postload glucose of ≤155 mg/dL.Abnormal glucose tolerance is highly prevalent in obese Thai youth. Several fasting indices and HbA1c fail to predict IGT. An 1-h OGTT glucose of >155 mg/dL appears to be more associated with adverse insulin dynamics and metabolic profile than 2-h postload glucose.

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Compound 18 Improves Glucose Tolerance in a Hepatocyte TGR5-dependent Manner in Mice

Nutrients ◽

10.3390/nu12072124 ◽

2020 ◽

Vol 12 (7) ◽

pp. 2124 ◽

Cited By ~ 2

Author(s):

Marlena M. Holter ◽

Margot K. Chirikjian ◽

Daniel A. Briere ◽

Adriano Maida ◽

Kyle W. Sloop ◽

...

Keyword(s):

Body Weight ◽

Glucose Tolerance ◽

Glucose Homeostasis ◽

Tolerance Test ◽

Whole Body ◽

Glucose Regulation ◽

Oral Glucose ◽

Dependent Manner ◽

Knockout Mouse Model ◽

Mouse Hepatocytes

The bile acid receptor, TGR5, is a key regulator of glucose homeostasis, but the mechanisms by which TGR5 signaling improves glucose regulation are incompletely defined. In particular, TGR5 has an increasingly appreciated role in liver physiology and pathobiology; however, whether TGR5 signaling within the liver contributes to its glucoregulatory effects is unknown. Therefore, we investigated the role of hepatocyte TGR5 signaling on glucose regulation using a hepatocyte-specific TGR5 knockout mouse model. Hepatocyte-specific Tgr5Hep+/+ and Tgr5Hep−/− mice were fed a high fat diet (HFD) for 7 weeks and then orally gavaged with three doses of a highly potent, TGR5-specific agonist, Compound 18 (10 mg/kg), or vehicle, over 72 h and underwent an oral glucose tolerance test (OGTT) after the last dose. Herein, we report that TGR5 mRNA and protein is present in mouse hepatocytes. Cumulative food intake, body weight, and adiposity do not differ between Tgr5Hep+/+ and Tgr5Hep−/− mice with or without treatment with Compound 18. However, administration of Compound 18 improves glucose tolerance in Tgr5HEP+/+ mice, but not in Tgr5Hep−/− mice. Further, this effect occurred independent of body weight and GLP-1 secretion. Together, these data demonstrate that TGR5 is expressed in hepatocytes, where it functions as a key regulator of whole-body glucose homeostasis.

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