Growth hormone controls lipolysis by regulation of FSP27 expression.
Growth hormone controls lipolysis by regulation of FSP27 expression.
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DOI：
10.1530/joe-18-0282
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发表时间：
2018-12-01
期刊：
影响因子：
--
通讯作者：
Lee KY
中科院分区：
文献类型：
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作者：
Sharma R;Luong Q;Sharma VM;Harberson M;Harper B;Colborn A;Berryman DE;Jessen N;Jørgensen JOL;Kopchick JJ;Puri V;Lee KY
人们早就知道生长激素 (GH) 会刺激脂肪分解和胰岛素抵抗；然而，这些效应背后的分子机制尚不清楚。在本研究中，我们证明 GH 会急剧诱导培养的脂肪细胞中的脂肪分解。这种效应是由于脂解负调节因子脂肪特异性蛋白 27 (FSP27) 在 mRNA 和蛋白质水平上的表达减少所致。这些效应在体内被模拟，因为 GH 的转基因过度表达会导致 FSP27 表达减少。从机制上讲，我们发现 GH 对 FSP27 表达的调节是通过激活 MEK/ERK 和 STAT5 依赖的细胞内信号传导来介导的。这两条分子途径相互作用，以差异化方式操纵 FSP27 启动子上的过氧化物酶体增殖物激活受体 γ 活性 (PPARγ)。此外，FSP27 的过度表达足以完全抑制培养脂肪细胞中 GH 诱导的脂肪分解和胰岛素抵抗。总而言之，这些数据揭示了 GH 敏锐调节脂肪细胞中的脂肪分解和胰岛素抵抗的分子机制。
Growth hormone (GH) has long been known to stimulate lipolysis and insulin resistance; however, the molecular mechanisms underlying these effects are unknown. In the present study, we demonstrate that GH acutely induces lipolysis in cultured adipocytes. This effect is secondary to the reduced expression of a negative regulator of lipolysis, Fat Specific Protein 27 (FSP27) at both the mRNA and protein level. These effects are mimicked in vivo as transgenic over-expression of GH leads to a reduction of FSP27 expression. Mechanistically, we show GH modulation of FSP27 expression is mediated through activation of both MEK/ERK and STAT5 dependent intracellular signaling. These two molecular pathways interact to differentially manipulate peroxisome proliferator-activated receptor gamma activity (PPARγ) on the FSP27 promoter. Furthermore, over-expression of FSP27 is sufficient to fully suppress GH-induced lipolysis and insulin resistance in cultured adipocytes. Taken together, these data decipher a molecular mechanism by which GH acutely regulates lipolysis and insulin resistance in adipocytes.