Matsuzaka Takashi, Shimano Hitoshi
Department of Internal Medicine, University of Tsukuba, Tennodai, Ibaraki, Japan.
J Mol Med (Berl). 2009 Apr;87(4):379-84. doi: 10.1007/s00109-009-0449-0. Epub 2009 Mar 4.
Obesity is a major health problem in industrialized societies often associated with diabetes, insulin resistance, and hepatic steatosis. This review addresses the hypothesis that elongation of long-chain fatty acids family member 6 (Elovl6) has an important role in energy metabolism and insulin sensitivity. Elovl6 is a microsomal enzyme involved in the elongation of saturated and monounsaturated fatty acids with 12, 14, and 16 carbons. Mice with targeted disruption in the gene for Elovl6 (Elovl6 (-/-)) are resistant to diet-induced insulin resistance despite their hepatosteatosis and obesity being similar to that of the wild-type mice. Protection against diet-induced insulin resistance in Elovl6 (-/-) mice is partially due to restoration of hepatic insulin receptor substrate-2 and suppression of hepatic protein kinase C epsilon, resulting in restoration of Akt phosphorylation. We suggest that inhibition of this elongase could be a new therapeutic approach for the treatment of insulin resistance, diabetes, cardiovascular disease, and other metabolic diseases.
肥胖是工业化社会中的一个主要健康问题，常与糖尿病、胰岛素抵抗和肝脂肪变性相关。本综述探讨了长链脂肪酸延长酶家族成员6（Elovl6）在能量代谢和胰岛素敏感性中起重要作用这一假说。Elovl6是一种微粒体酶，参与12、14和16碳饱和及单不饱和脂肪酸的延长。Elovl6基因靶向敲除的小鼠（Elovl6（-/-））尽管肝脂肪变性和肥胖程度与野生型小鼠相似，但对饮食诱导的胰岛素抵抗具有抗性。Elovl6（-/-）小鼠对饮食诱导的胰岛素抵抗的保护作用部分归因于肝脏胰岛素受体底物-2的恢复和肝脏蛋白激酶Cε的抑制，从而导致Akt磷酸化的恢复。我们认为，抑制这种延长酶可能是治疗胰岛素抵抗、糖尿病、心血管疾病和其他代谢性疾病的一种新的治疗方法。
