Abstract
In non‐athletes, insulin sensitivity correlates negatively with intramyocellular lipid (IMCL) content. In athletes, however, a pattern of benign IMCL storage exists, which is characterized by lipid storage in type I muscle fibres, in small and numerous lipid droplets (LDs) preferable coated with PLIN5, without affecting insulin sensitivity. Administration of resveratrol has been promoted for its beneficial effects on glucose homeostasis. We observed that 30 days of oral resveratrol administration (150 mg/day) in metabolically compromised individuals showed a 33% increase in IMCL (placebo vs. resveratrol; 0.86 ± 0.090 AU vs. 1.14 ± 0.11 AU, p = 0.003) without impeding insulin sensitivity. Thus, the aim of the present study was to examine if a resveratrol‐mediated increase in IMCL content, in metabolically compromised individuals, changes the LD phenotype towards the phenotype we previously observed in athletes. For this, we studied IMCL, LD number, LD size, subcellular distribution and PLIN5 coating in different fibre types using high‐resolution confocal microscopy. As proof of concept, we observed a 2.3‐fold increase (p = 0.038) in lipid accumulation after 48 h of resveratrol incubation in cultured human primary muscle cells. In vivo analysis showed that resveratrol‐induced increase in IMCL is predominantly in type I muscle fibres (placebo vs. resveratrol; 0.97 ± 0.16% vs. 1.26 ± 0.09%; p = 0.030) in both the subsarcolemmal (p = 0.016) and intermyofibrillar region (p = 0.026) and particularly in PLIN5‐coated LDs (p = 0.024). These data indicate that administration of resveratrol augments IMCL content in metabolically compromised individuals towards a LD phenotype that mimics an ‘athlete like phenotype’.
Highlights
Compromised insulin-mediated glucose uptake in muscle is commonly observed in middle-aged, overweight individuals and is a hallmark in the pathogenesis of insulin resistance and type 2 diabetes mellitus (T2DM) development (DeFronzo & Tripathy, 2009)
We examined if resveratrol-induced elevation of intramyocellular lipid (IMCL) after 30 days of in vivo resveratrol supplementation changed the morphological characteristics of myocellular lipid droplets (LDs) such that they mimic the profile of lipid storage previously observed in athletes
The current study showed that resveratrol augments IMCL content in human skeletal muscle and results in remodelling of LDs in a cell autonomous fashion
Summary
Compromised insulin-mediated glucose uptake in muscle is commonly observed in middle-aged, overweight individuals and is a hallmark in the pathogenesis of insulin resistance and type 2 diabetes mellitus (T2DM) development (DeFronzo & Tripathy, 2009). This has triggered the search for drug or nutritional interventions that mimic the effects of caloric restriction and/or exercise In this respect, the polyphenol resveratrol is of interest as it promotes mitochondrial function and metabolic health in model systems via SIRT1 and PGC1α (Lagouge et al, 2006). Administration of 150 mg transresveratrol daily for 30 days was performed in three populations; middle aged normoglycaemic obese individuals (Timmers et al, 2011), middle-aged overweight first-degree relatives of patients with T2DM with compromised glucose homeostasis (de Ligt et al, 2018) and patients with T2DM (Timmers et al, 2016) In these studies, resveratrol administration consistently improved mitochondrial function while the effects on markers of insulin sensitivity were less consistent. We examined if resveratrol-induced elevation of IMCL after 30 days of in vivo resveratrol supplementation changed the morphological characteristics of myocellular LDs such that they mimic the profile of lipid storage previously observed in athletes
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