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Background: Dihydrocapsiate is a capsinoid found in chili peppers. Dihydrocapsiate is similar to capsaicin, which is known for its thermogenic properties. Objective: The objective was to determine the acute and chronic effect of dihydrocapsiate on resting metabolic rate (RMR). Design: Seventy-eight healthy subjects in a double-blind, parallel-arm trial were randomly assigned to 3 groups receiving 0 (placebo), 3, or 9 mg dihydrocapsiate/d for 28 d. After a 10-h overnight fast, RMR was measured by indirect calorimetry for 30 min before and 120 min after ingestion of dihydrocapsiate. Results: RMR was similar in the 3 groups before dosing on day 1 [1714 [+ or -] 41 kcal/d (0 mg), 1760 [+ or -] 41 kcal/d (3 mg), and 1694 [+ or -] 38 kcal/d (9 mg)] and after acute dosing (41 [+ or -] 17, 55 [+ or -] 17, and 3 [+ or -] 24 kcal/d for 3-mg, 9-mg, and placebo groups, respectively). When the chronic effect of dihydrocapsiate on RMR was calculated from the average 2-h RMR on day 28 minus the 30-min preingestion RMR at baseline, a borderline effect in subjects receiving 3 mg dihydrocapsiate/d compared with placebo was observed (61 [+ or -] 24 kcal/d compared with - 1 [+ or -] 12 kcal/d, P = 0.054), whereas no significant increase in RMR in comparison with placebo was noted for the 9-mg/d dose (48 [+ or -] 23 kcal/d compared with - 1 [+ or -] 12 kcal/d, P = 0.12). When data from both groups were combined, the thermic effect of dihydrocapsiate reached significance (53 [+ or -] 9 kcal/d compared with -1 [+ or -] 12 kcal/d in the placebo group, P = 0.04). Fat oxidation was unaffected by dihydrocapsiate. Conclusion: After 1 mo of supplementation, dihydrocapsiate had a small thermogenic effect of [approximately equal to] 50 kcal/d, which is in the range of day-to-day RMR variability. This trial was registered at clinical-trials. gov as NCT00999297. doi: 10.3945/ajcn.2010.30036

OBJECTIVE--Compared with nondiabetic subjects, type 2 diabetic subjects are metabolically inflexible with impaired fasting fat oxidation and impaired carbohydrate oxidation during a hyperinsulinemic clamp. We hypothesized that impaired insulin-stimulated glucose oxidation is a consequence of the lower cellular glucose uptake rate in type 2 diabetes. Therefore, we compared metabolic flexibility to glucose adjusted for glucose disposal rate in nondiabetic versus type 2 diabetic subjects and in the latter group after 1 year of lifestyle intervention (the Look AHEAD [Action For Health in Diabetes] trial). RESEARCH DESIGN AND METHODS--Macronutrient oxidation rates under fasting and hyperinsulinemic conditions (clamp at 80 mU/[m.sup.2] per min), body composition (dual-energy X-ray absorptiometry), and relevant hormonal/metabolic blood variables were assessed in 59 type 2 diabetic and 42 nondiabetic individuals matched for obesity, sex, and race. Measures were repeated in diabetic participants after weight loss. RESULTS--Metabolic flexibility to glucose (change in respiratory quotient [RQ]) was mainly related to insulin-stimulated glucose disposal rate ([R.sup.2] = 0.46, P < 0.0001) with an additional 3% of variance accounted for by plasma free fatty acid concentration at the end of the clamp (P = 0.03). The impaired metabolic flexibility to glucose observed in type 2 diabetic versus nondiabetic subjects (ΔRQ 0.06 ± 0.01 vs. 0.10 ± 0.01, respectively, P < 0.0001) was no longer observed after adjusting for glucose disposal rate (P = 0.19). Additionally, the increase in metabolic flexibility to glucose after weight loss was accounted for by the concomitant increase in insulin-stimulated glucose disposal rate. CONCLUSIONS--This study suggests that metabolic inflexibility to glucose in type 2 diabetic subjects is mostly related to defective glucose transport., Metabolic flexibility is the capacity of the body to match fuel oxidation to fuel availability. It is typically assessed by the increase in respiratory quotient (RQ) from fasting to glucose/ [...]

A recent study by Zhou and colleagues proposed that low metabolic elasticity and gene elasticity are involved in the metabolic alterations observed in ageing and obesity. Here, we discuss some of their findings to provide a viewpoint on these potential new traits associated with metabolic health.

Endurance exercise has been shown to improve lipid oxidation and increase mitochondrial content in skeletal muscle, two features that have shown dependence on increased expression of the peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α). It is also hypothesized that exercise-related alterations in PGC1α expression occur through epigenetic regulation of nucleosome positioning in association with differential DNA methylation status within the PGC1α promoter. In this study, we show that when primary human myotubes from obese patients with type 2 diabetes are exposed to lipolytic stimulus (palmitate, forskolin, inomycin) in vitro, nucleosome occupancy surrounding the -260 nucleotide (nt) region, a known regulatory DNA methylation site, is reduced. This finding is reproduced in vivo in the vastus lateralis from 11 healthy males after a single, long endurance exercise bout in which participants expended 650 kcal. Additionally, we show a significant positive correlation between fold change of PGC1α messenger RNA expression and -1 nucleosome repositioning away from the -260 nt methylation site in skeletal muscle tissue following exercise. Finally, we found that when exercise participants are divided into high and low responders based on the -260 nt methylation status, the -1 nucleosome is repositioned away from the regulatory -260 nt methylation site in high responders, those exhibiting a significant decrease in -260 nt methylation, but not in low responders. Additionally, high but not low responders showed a significant decrease in intramyocellular lipid content after exercise. These findings suggest a potential target for epigenetic modification of the PGC1α promoter to stimulate the therapeutic effects of endurance exercise in skeletal muscle.