Hormone-sensitive lipase modulates adipose metabolism through PPARγ
Hormone-sensitive lipase modulates adipose metabolism through PPARγ
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DOI：
10.1016/j.bbalip.2010.10.001
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发表时间：
2011-01-01
影响因子：
4.8
通讯作者：
Kraemer, Fredric B.
中科院分区：
文献类型：
--
作者：
Shen, Wen-Jun;Yu, Zaixin;Kraemer, Fredric B.
激素敏感性脂肪酶（HSL）是脂肪组织中甘油二酯和胆固醇酯水解的限速酶，对完全脂肪酸刺激的脂解是必不可少的。HSL-/-小鼠的基因表达谱表明，HSL是重要的调节脂肪形成和脂肪代谢。为了测试是否需要HSL来供应用于正常脂肪分化的PPAR γ的内在配体，向HSL-/-和野生型（WT）同窝仔饲喂补充有或没有罗格列酮（200 mg/kg）的正常食物（NC）和高脂肪（HF）饮食16周。结果显示，将罗格列酮补充到NC饮食中完全使HSL-/-小鼠中降低的体重和脂肪库正常化。此外，罗格列酮导致WT和HSL-/-小鼠的血清葡萄糖、总胆固醇、FFA和脂联素值相似。此外，罗格列酮使HSL-/-小鼠中脂肪细胞分化相关基因、脂肪细胞分化标志物、三酰甘油合成和代谢相关酶以及胆固醇酯稳态的表达正常化。在HF饮食中补充罗格列酮导致WT和HSL-/-动物的葡萄糖耐量改善，并且HSL-/-小鼠的异常WAT基因表达、血清化学、器官和体重变化部分正常化。体外研究表明，来自WT动物的脂肪细胞可以提供激活PPAR γ的配体，并且在脂解刺激后激活进一步增强，而来自HSL-/-小鼠的脂肪细胞显示出减弱的PPAR γ激活，在脂解刺激后没有变化。这些结果表明，HSL调节脂肪代谢的机制之一是通过提供内源性配体或前配体的过氧化物酶体增殖物激活受体γ。由爱思唯尔公司出版
Hormone-sensitive lipase (HSL) is rate limiting for diacylglycerol and cholesteryl ester hydrolysis in adipose tissue and essential for complete hormone-stimulated lipolysis. Gene expression profiling in HSL-/- mice suggests that HSL is important for modulating adipogenesis and adipose metabolism. To test whether HSL is required for the supply of intrinsic ligands for PPAR gamma for normal adipose differentiation, HSL-/- and wildtype (WT) littermates were fed normal chow (NC) and high-fat (HF) diets supplemented with or without rosiglitazone (200 mg/kg) for 16 weeks. Results show that supplementing rosiglitazone to an NC diet completely normalized the decreased body weight and adipose depots in HSL-/- mice. Additionally, rosiglitazone resulted in similar serum glucose, total cholesterol, FFA, and adiponectin values in WT and HSL-/- mice. Furthermore, rosiglitazone normalized the expression of genes involved in adipocyte differentiation, markers of adipocyte differentiation, and enzymes involved in triacylglycerol synthesis and metabolism, and cholesteryl ester homeostasis, in HSL-/- mice. Supplementing rosiglitazone to an HF diet resulted in improved glucose tolerance in both WT and HSL-/- animals and also partial normalization in HSL-/- mice of abnormal WAT gene expression, serum chemistries, organ and body weight changes. In vitro studies showed that adipocytes from WT animals can provide ligands for activation of PPAR gamma and that activation is further boosted following lipolytic stimulation, whereas adipocytes from HSL-/- mice displayed attenuated activation of PPAR gamma, with no change following lipolytic stimulation. These results suggest that one of the mechanisms by which HSL modulates adipose metabolism is by providing intrinsic ligands or pro-ligands for PPAR gamma. Published by Elsevier B.V.