Insulin and glucocorticoids differentially regulate leptin transcription and secretion in brown adipocytes
Insulin and glucocorticoids differentially regulate leptin transcription and secretion in brown adipocytes
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DOI：
10.1096/fj.00-0669com
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发表时间：
2001-06-01
期刊：
影响因子：
4.8
通讯作者：
Lombès, M
中科院分区：
文献类型：
--
作者：
Buyse, M;Viengchareun, S;Lombès, M
瘦素是ob基因的产物，由脂肪组织产生，受到复杂的激素和代谢调节。瘦素在体重平衡中起着至关重要的作用。在这里，我们报告了棕色脂肪细胞对瘦素的分泌和激素调节。利用最近建立的T37i细胞系，我们发现瘦素的表达和分泌是细胞分化的函数。在分化的T37i细胞中，胰岛素以浓度依赖的方式(EC50=0.1 nM)诱导瘦素的释放(类似于0.25 ng/10(6)细胞/小时)，这一作用可被β3-肾上腺素能配体、噻唑烷二酮、放线菌亚胺或放线菌素D完全抑制。胰岛素诱导瘦素mRNA水平强烈、快速(在2小时内)但短暂地增加5倍。胰岛素对ob基因表达的这种转录调控涉及磷脂酰肌醇3-激酶和MAP激酶依赖的途径。糖皮质激素抑制胰岛素刺激的瘦素分泌和ob基因表达，但不影响瘦素mRNA的稳定性(t(1/2)=3h05)。总之，我们的结果表明，棕色脂肪细胞表达和分泌瘦素，其激素调节明显不同于白色脂肪组织中所描述的。这些发现指出了组织特有的分子机制，并表明瘦素可能通过自分泌机制对能量稳态产生直接影响。
Leptin, the ob gene product, is produced by adipose tissue and is submitted to a complex hormonal and metabolic regulation. Leptin plays a critical role in the balance of body weight. Here we report on secretion and hormonal regulation of leptin by brown adipocytes. Using the recently established T37i cell line, we show that leptin expression and secretion occurred as a function of cell differentiation. In differentiated T37i cells, insulin induced leptin release (similar to0.25 ng/10(6) cells/h) in a concentration-dependent manner (EC50=0.1 nM), and this was totally suppressed by beta3 -adrenergic ligand, thiazolidinedione, cycloheximide, or actinomycin D. Insulin induced a strong, rapid (within 2 h) but transient fivefold increase in leptin mRNA levels. This transcriptional control of ob gene expression by insulin involved both phosphatidylinositol 3-kinase- and MAP kinase-dependent pathways. Glucocorticoids inhibited both insulin-stimulated leptin secretion and ob gene expression without affecting leptin mRNA stability (t(1/2)=3h05). Altogether, our results demonstrate that brown adipocytes express and secrete leptin, whose hormonal regulation clearly differs from that described in white adipose tissue. These findings point to tissue-specific molecular mechanisms and suggest that leptin might exert direct effects on energy homeostasis through an autocrine mechanism.