Resveratrol improves ex vivo mitochondrial function but does not affect insulin sensitivity or brown adipose tissue in first degree relatives of patients with type 2 diabetes

Abstract

ObjectiveResveratrol supplementation improves metabolic health in healthy obese men, but not in patients with type 2 diabetes (T2D) when given as add-on therapy. Therefore, we examined whether resveratrol can enhance metabolic health in men at risk of developing T2D. Additionally, we examined if resveratrol can stimulate brown adipose tissue (BAT).MethodsThirteen male first degree relatives (FDR) of patients with T2D received resveratrol (150 mg/day) and placebo for 30 days in a randomized, placebo controlled, cross-over trial.ResultsResveratrol significantly improved ex vivo muscle mitochondrial function on a fatty acid-derived substrate. However, resveratrol did not improve insulin sensitivity, expressed as the rate of glucose disposal during a two-step hyperinsulinemic-euglycemic clamp. Also, intrahepatic and intramyocellular lipid content, substrate utilization, energy metabolism, and cold-stimulated 18F-FDG glucose uptake in BAT (n = 8) remained unaffected by resveratrol. In vitro experiments in adipocytes derived from human BAT confirmed the lack of effect on BAT.ConclusionsResveratrol stimulates muscle mitochondrial function in FDR males, which is in concordance with previous results. However, no other metabolic benefits of resveratrol were found in this group. This could be attributed to subject characteristics causing alterations in metabolism of resveratrol and thereby affecting resveratrol's effectiveness.ClinicalTrials.gov IDNCT02129595.

TSH suppression aggravates arterial inflammation — an 18F-FDG PET study in thyroid carcinoma patients

“…As euthyroid controls, we used data from placebo scans of eight participants of a crossover study evaluating the effect of resveratrol supplementation on BAT activation in subjects at risk of developing type 2 diabetes [ 15 ]. Participants had no known history of thyroid disease or medication that could interfere with thyroid hormones.…”

“…All subjects underwent the same PET scan protocol which included an overnight fast, a dedicated and personalized cooling protocol, and the injection of a fixed activity of approximately 75 MBq 18 F-FDG (details can be found in Broeders et al [ 14 ] and de Ligt et al [ 15 ]). Imaging was performed using a Gemini™ TF PET/CT system (Philips Healthcare, Eindhoven, The Netherlands).…”

Altered mitochondrial metabolism in the insulin‐resistant heart

“…Although treatment with resveratrol has shown promising results in preclinical studies, no effect of resveratrol was observed on different markers of cardiovascular disease risk in ageing and obese individuals . Recent studies have demonstrated that resveratrol supplementation improves skeletal muscle mitochondrial function, however, it does not improve insulin sensitivity in people at risk of or with T2DM . Further studies aiming to understand resveratrol metabolism and pharmacokinetics, may therefore be required to realize the therapeutic potential of this approach.…”

“…310 Recent studies have demonstrated that resveratrol supplementation improves skeletal muscle mitochondrial function, however, it does not improve insulin sensitivity in people at risk of or with T2DM. 311,312 Further studies aiming to understand resveratrol metabolism and pharmacokinetics, may therefore be required to realize the therapeutic potential of this approach.…”

One-leg inactivity induces a reduction in mitochondrial oxidative capacity, intramyocellular lipid accumulation and reduced insulin signalling upon lipid infusion: a human study with unilateral limb suspension

“…Data are presented as mean ± SEM. The samples size was determined based on insulin-stimulated skeletal muscle glucose disposal, with the expected effect size and SD based on previous research within our research group [44]. All statistics were performed using SPSS 16.0 for Mac (IBM, New York, NY, USA).…”