基于AMPK信号通路研究Omega-7棕榈油酸调控糖脂代谢的激素样作用及分子机制

棕榈油酸是一种Omega-7单不饱和脂肪酸，主要来源于硬脂酰辅酶A去饱和酶-1（SCD-1）调控的脂质生成作用。棕榈油酸可由脂肪组织分泌，并参与调节远隔器官的糖脂代谢，该特性与脂肪细胞因子等蛋白类激素相似，因此棕榈油酸被认为一种可能的新型“脂质激素”。然而由于膳食和内源性合成因素的相互干扰，棕榈油酸调控糖脂代谢的激素样作用仍有待验证，相关分子机制尚不明确。本项目拟构建脂肪组织SCD-1基因特异性敲除小鼠模型，在脂肪组织棕榈油酸内源性合成受损条件下，探究外源性棕榈油酸对高脂饮食小鼠脂肪细胞因子表达及对远隔器官糖脂代谢的影响，从而验证棕榈油酸调控糖脂代谢的激素样作用；探究棕榈油酸对AMPK及下游信号通路中糖脂代谢相关基因和蛋白表达的影响，并利用AMPK抑制剂验证棕榈油酸调控糖脂代谢是否依赖于AMPK。本研究将全面揭示棕榈油酸调控糖脂代谢的激素样作用及分子机制，为肥胖相关代谢紊乱防治提供新思路。

The palmitoleic acid is one kind of omega-7 monounsaturated fatty acids, and mainly derives from de novo lipogenesis mediated by stearoyl-CoA desaturase-1 (SCD-1) in humans and animals. Palmitoleic acid could be released by adipose tissue, and affect the glucose and lipid metabolism of distant organs which mimics the role of adipokines, thus it was identified as a novel lipid hormone “Lipokine”. However, due to the complicate interaction between diet and endogenous synthesis of palmitoleic acid, the hormone-like effects of palmitoleic acid on glucose and lipid metabolism need to be confirmed, and the underlying mechanisms remains largely unclear. Therefore, we intended to use adipose tissue-specific SCD-1 gene knockout mice (Adipo-SCD-1-/- mice), to investigate the effects of exogenous palmitoleic acid supplementation on adipokines secretion and glucose and lipid metabolism in high-fat diet fed Adipo-SCD-1-/- mice. We will also investigate the effect of palmitoleic acid on the expressions of key genes and proteins that are related to glucose or lipid metabolism, and verify whether palmitoleic acid affecting glucose or lipid metabolism is dependent of AMPK by intervening mice AMPK inhibitor. The present study aimed to elucidate the hormone-like effects of palmitoleic acid on glucose and lipid metabolism and related mechanism, and further provide a new strategy for the prevention and treatment of obesity-related metabolic disorders.