Kievit Paul, Howard Jane K, Badman Michael K, Balthasar Nina, Coppari Roberto, Mori Hiroyuki, Lee Charlotte E, Elmquist Joel K, Yoshimura Akihiko, Flier Jeffrey S
Division of Endocrinology, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, Massachusetts 02215, USA.
Cell Metab. 2006 Aug;4(2):123-32. doi: 10.1016/j.cmet.2006.06.010.
Suppressor of cytokine signaling-3 (Socs-3) negatively regulates the action of various cytokines, as well as the metabolic hormones leptin and insulin. Mice with haploinsufficiency of Socs-3, or those with neuronal deletion of Socs-3, are lean and more leptin and insulin sensitive. To examine the role of Socs-3 within specific neurons critical to energy balance, we created mice with selective deletion of Socs-3 within pro-opiomelanocortin (POMC)-expressing cells. These mice had enhanced leptin sensitivity, measured by weight loss and food intake after leptin infusion. On chow diet, glucose homeostasis was improved despite normal weight gain. On a high-fat diet, the rate of weight gain was reduced, due to increased energy expenditure rather than decreased food intake; glucose homeostasis and insulin sensitivity were substantially improved. These studies demonstrate that Socs-3 within POMC neurons regulates leptin sensitivity and glucose homeostasis, and plays a key role in linking high-fat diet to disordered metabolism.
细胞因子信号转导抑制因子3（Socs-3）对多种细胞因子以及代谢激素瘦素和胰岛素的作用具有负向调节作用。Socs-3单倍体不足的小鼠，或神经元中Socs-3缺失的小鼠，体型偏瘦，对瘦素和胰岛素更敏感。为了研究Socs-3在对能量平衡至关重要的特定神经元中的作用，我们培育了在表达阿黑皮素原（POMC）的细胞中选择性缺失Socs-3的小鼠。通过输注瘦素后的体重减轻和食物摄入量来衡量，这些小鼠的瘦素敏感性增强。在普通饮食条件下，尽管体重正常增加，但葡萄糖稳态得到改善。在高脂饮食条件下，体重增加速率降低，这是由于能量消耗增加而非食物摄入量减少所致；葡萄糖稳态和胰岛素敏感性得到显著改善。这些研究表明，POMC神经元中的Socs-3调节瘦素敏感性和葡萄糖稳态，并在将高脂饮食与代谢紊乱联系起来方面起关键作用。
