Adipocyte lipases and defect of lipolysis in human obesity
Adipocyte lipases and defect of lipolysis in human obesity
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DOI：
10.2337/diabetes.54.11.3190
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发表时间：
2005-11-01
期刊：
影响因子：
7.7
通讯作者：
Arner, P
中科院分区：
文献类型：
--
作者：
Langin, D;Dicker, A;Arner, P
储存在脂肪组织中的脂肪的动员是由激素敏感脂肪酶（HSL）和最近发现的脂肪甘油三酯脂肪酶（ATGL）介导的，但它们在脂肪分解中的相对重要性尚不清楚。我们证明了一种新的有效的HSL抑制剂不抑制其他脂肪酶。该化合物抵消了儿茶酚胺刺激的小鼠脂肪细胞的脂肪分解，对HSL-null小鼠的残余甘油三酯水解和脂肪分解没有影响。在人脂肪细胞中，儿茶酚胺和利钠肽诱导的脂肪分解被HSL抑制剂完全钝化。当脂肪细胞不受刺激时，甘油而非脂肪酸的释放被抑制。在脂肪细胞分化过程中，HSL和ATGL mRNA水平同时升高。人类脂肪组织中这两个转录本的丰度在习惯饮食条件和低热量饮食期间高度相关，表明这两个基因有共同的调节机制。肥胖和非肥胖受试者的比较表明，肥胖与成熟脂肪细胞和分化前脂肪细胞中儿茶酚胺诱导的脂肪分解和HSL表达减少有关。总之，HSL是儿茶酚胺和利钠肽刺激的脂肪分解的主要脂肪酶，而ATGL在基础脂肪分解过程中介导甘油三酯的水解。儿茶酚胺诱导的脂肪分解减少和低HSL表达可能是肥胖的主要缺陷。
The mobilization of fat stored in adipose tissue is mediated by hormone-sensitive lipase (HSL) and the recently characterized adipose triglyceride lipase (ATGL), yet their relative importance in lipolysis is unknown. We show that a novel potent inhibitor of HSL does not inhibit other lipases. The compound counteracted catecholamine-stimulated lipolysis in mouse adipocytes and had no effect on residual triglyceride hydrolysis and lipolysis in HSL-null mice. In human adipocytes, catecholamine- and natriuretic peptide-induced lipolysis were completely blunted by the HSL inhibitor. When fat cells were not stimulated, glycerol but not fatty acid release was inhibited. HSL and ATGL mRNA levels increased concomitantly during adipocyte differentiation. Abundance of the two transcripts in human adipose tissue was highly correlated in habitual dietary conditions and during a hypocaloric diet, suggesting common regulatory mechanisms for the two genes. Comparison of obese and nonobese subjects showed that obesity was associated with a decrease in catecholamine-induced lipolysis and HSL expression in mature fat cells and in differentiated preadipocytes. In conclusion, HSL is the major lipase for catecholamine- and natriuretic peptide-stimulated lipolysis, whereas ATGL mediates the hydrolysis of triglycerides during basal lipolysis. Decreased catecholamine-induced lipolysis and low HSL expression constitute a possibly primary defect in obesity.