Department of Metabolic Diseases, Medical University of Bialystok, Bialystok, Poland.
Department of Prophylaxis of Metabolic Diseases, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, Olsztyn, Poland.
Endocrine. 2018 May;60(2):263-271. doi: 10.1007/s12020-018-1544-1. Epub 2018 Feb 7.
Sirtuin 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.
We 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.
Obese 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.
Adipose 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.
Sirtuin 1 可能调节葡萄糖和脂质代谢。我们旨在评估与胰岛素敏感性、促炎和代谢基因表达相关的脂肪组织和骨骼肌 Sirtuin 1 表达，并研究高胰岛素血症和循环游离脂肪酸升高对 Sirtuin 1 表达的调节作用。
我们检查了 60 名正常体重、42 名超重和 15 名肥胖的年轻受试者。应用高胰岛素-正常血糖钳夹技术来测量胰岛素敏感性。在 20 名受试者中，进行了两次 6 小时的钳夹，其中一次同时进行 Intralipid/肝素输注。采集皮下脂肪组织和骨骼肌活检标本，用于基因和蛋白表达的测量。
与正常体重和超重参与者相比，肥胖受试者的脂肪组织 Sirtuin 1 水平较低。肌肉 Sirtuin 1 在各组之间没有差异。脂肪组织 Sirtuin 1 与胰岛素敏感性、脂肪组织 SLC2A4 相关。在控制 BMI 后，脂肪组织 Sirtuin 1 与胰岛素敏感性的关系仍然存在，但在控制脂肪组织 SLC2A4 后，这种关系消失。肌肉 Sirtuin 1 与胰岛素敏感性无关。高胰岛素血症降低了脂肪组织和增加了肌肉 Sirtuin 1 表达。Intralipid/肝素输注否定了这些影响。
脂肪组织而非肌肉 Sirtuin 1 与人类胰岛素敏感性相关，这可能是由于其与脂肪组织 SLC2A4 表达相关。胰岛素短期差异调节脂肪组织和骨骼肌 Sirtuin 1 表达，而循环游离脂肪酸升高则否定了这些作用，这可能与脂质诱导的胰岛素抵抗有关。
