Abstract
Epidemiological studies pointed out to a strong association between vitamin D deficiency and type 2 diabetes prevalence. However, the role of vitamin D supplementation in the skeletal muscle, a tissue that play a crucial role in the maintenance of glucose homeostasis, has been scarcely investigated so far. On this basis, this study aimed to evaluate the effect of vitamin D supplementation in a murine model of diet-induced insulin resistance with particular attention to the effects evoked on the skeletal muscle. Male C57BL/6J mice (n = 40) were fed with a control or a High Fat-High Sugar (HFHS) diet for 4 months. Subsets of animals were treated for 2 months with vitamin D (7 μg·kg-1, i.p. three times/week). HFHS diet induced body weight increase, hyperglycemia and impaired glucose tolerance. HFHS animals showed an impaired insulin signaling and a marked fat accumulation in the skeletal muscle. Vitamin D reduced body weight and improved systemic glucose tolerance. In addition, vitamin D restored the impaired muscle insulin signaling and reverted myosteatosis evoked by the diet. These effects were associated to decreased activation of NF-κB and lower levels of TNF-alpha. Consistently, a significantly decreased activation of the SCAP/SREBP lipogenic pathway and lower levels of CML protein adducts and RAGE expression were observed in skeletal muscle of animals treated with vitamin D.Collectively, these data indicate that vitamin D-induced selective inhibition of signaling pathways (including NF-κB, SCAP/SREBP and CML/RAGE cascades) within the skeletal muscle significantly contributed to the beneficial effects of vitamin D supplementation against diet-induced metabolic derangements.
Highlights
Vitamin D is a prohormon with multiple functions that extend beyond the regulation of the intestinal calcium absorption
Results from preclinical studies showed that vitamin D administration reduced the levels of blood glucose and improved insulin sensitivity in diabetic mice [12], attenuated the fibrosis and the increased expression of the receptor for advanced glycation end products (RAGE) in hearts of diabetic rats, and improved high fat diet-induced metabolic syndrome and reduced hepatic steatosis in rats [13, 14]
The factors leading to accumulation of intra- and intermuscular fat, a phenomenon known as myosteatosis, are not well understood, we suggested that the accumulation of advanced glycations end products (AGEs) is the possible molecular mechanism linking the impairment of insulin sensitivity to activation of lipogenesis and to changes in muscle fiber size and composition that occur in diet-induced obese mouse skeletal muscle [15, 16]
Summary
Vitamin D is a prohormon with multiple functions that extend beyond the regulation of the intestinal calcium absorption. Results from preclinical studies showed that vitamin D (or calcitriol) administration reduced the levels of blood glucose and improved insulin sensitivity in diabetic mice [12], attenuated the fibrosis and the increased expression of the receptor for advanced glycation end products (RAGE) in hearts of diabetic rats, and improved high fat diet-induced metabolic syndrome and reduced hepatic steatosis in rats [13, 14]. It may be hypothesized that the improvement of skeletal muscle insulin sensitivity induced by vitamin D can be paralleled by a reduction of diet-induced myosteatosis. The aim of the present study was to investigate whether vitamin D administration improves skeletal muscle insulin sensitivity and metabolic profile of diet-induced obese mice and whether these improvements could be associated to reduction of myosteatosis
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