Abstract
PurposeSirtuin 1 may regulate glucose and lipid metabolism. We aimed to assess adipose tissue and skeletal muscle sirtuin 1 expression in relation to insulin sensitivity, the expression of proinflammatory and metabolic genes, and to study the regulation of sirtuin 1 expression by hyperinsulinemia and circulating free fatty acids elevation.MethodsWe examined 60 normal-weight, 42 overweight and 15 obese young subjects. The hyperinsulinemic-euglycemic clamp technique was applied throughout to measure insulin sensitivity. In 20 subjects, two 6 h clamps were performed, one of them with concurrent Intralipid/heparin infusion. Biopsies of subcutaneous adipose tissue and skeletal muscle were collected for the measurement of gene and protein expression.ResultsObese subjects had lower adipose sirtuin 1 in comparison with normal-weight and overweight participants. Muscle sirtuin 1 did not differ between the groups. Adipose tissue sirtuin 1 was related to insulin sensitivity, adipose tissue SLC2A4. The relationship between adipose tissue sirtuin 1 and insulin sensitivity was still present after controlling for BMI, however, it disappeared after controlling for adipose tissue SLC2A4. Muscle sirtuin 1 was not related to insulin sensitivity. Hyperisulinemia decreased adipose tissue and increased muscle sirtuin 1 expression. Intralipid/heparin infusion negated these effects.ConclusionsAdipose tissue, but not muscle, sirtuin 1 is associated with insulin sensitivity in humans, possibly because of its correlation with adipose tissue SLC2A4 expression. Insulin differentially regulates adipose tissue and skeletal muscle sirtuin 1 expression in the short-term and circulating free fatty acids elevation negates these effects, which may be associated with lipid-induced insulin resistance.
Highlights
Sirtuin 1 (SIRT1), is a (NAD)-dependent deacetylase, a member of the sirtuin family [1]
We examined the regulation of tissue SIRT1 expression by hyperinsulinemia and circulating free fatty acids (FFA) elevation
IL18 and CCL2 AT expression was higher whereas SLC2A4 and ADIPOQ AT expression was lower in the obese than in normal-weight and overweight subjects
Summary
Sirtuin 1 (SIRT1), is a (NAD)-dependent deacetylase, a member of the sirtuin family [1]. SIRT1 may influence insulin signaling in multiple insulin sensitive cells [3]. It increases insulin receptor substrate 2 (IRS2) and protein kinase B (PKB, known as Akt) phosphorylation in response to insulin whereas it decreases the expression of protein-tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin signalling [4,5,6]. SIRT1 represses proinflammatory gene expression in adipocytes, possibly through nuclear factor κB (NFκB) deacetylation and inhibition of binding to its target gene promoters [8]. It increases adiponectin synthesis/secretion [9]
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