Wang Z, Zhou Y T, Kakuma T, Lee Y, Kalra S P, Kalra P S, Pan W, Unger R H
Gifford Laboratories, Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA.
Biochem Biophys Res Commun. 2000 Oct 14;277(1):20-6. doi: 10.1006/bbrc.2000.3615.
Liver-derived hyperleptinemia induced in normal rats by adenovirus-induced gene transfer causes rapid disappearance of body fat, whereas the endogenous adipocyte-derived hyperleptinemia of obesity does not. Here we induce liver-derived hyperleptinemia in rats with adipocyte-derived hyperleptinemia of acquired obesity caused by ventromedial hypothalamus lesioning (VMH rats) or by feeding 60% fat (DIO rats). Liver-derived hyperleptinemia in obese rats caused only a 5-7% loss of body weight, compared to a 13% loss in normoleptinemic lean animals; but in actual grams of weight lost there was no significant difference between obese and lean groups, suggesting that a subset of cells remain leptin-sensitive in obesity. mRNA and protein of a putative leptin-resistance factor, suppressor of cytokine signaling (SOCS)-1 or -3, were both increased in white adipose tissues (WAT) of VMH and DIO rats. Since transgenic overexpression of SOCS-3 in islets reduced the lipopenic effect of leptin by 75%, we conclude that the increased expression of SOCS-1 and -3 in WAT of rats with acquired obesity could have blocked leptin's lipopenic action in the leptin-resistant WAT population.
腺病毒介导的基因转移在正常大鼠中诱导产生的肝脏源性高瘦素血症会导致体脂快速消失，而肥胖症中内源性脂肪细胞源性高瘦素血症则不会。在此，我们在因腹内侧下丘脑损伤导致获得性肥胖的脂肪细胞源性高瘦素血症大鼠（VMH大鼠）或喂食60%脂肪的大鼠（饮食诱导肥胖大鼠，DIO大鼠）中诱导产生肝脏源性高瘦素血症。肥胖大鼠中的肝脏源性高瘦素血症仅导致体重减轻5 - 7%，而正常瘦素水平的瘦动物体重减轻13%；但就实际减轻的体重克数而言，肥胖组和瘦组之间没有显著差异，这表明肥胖症中有一部分细胞对瘦素仍敏感。在VMH大鼠和DIO大鼠的白色脂肪组织（WAT）中，一种假定的瘦素抵抗因子——细胞因子信号抑制因子（SOCS）-1或-3的mRNA和蛋白质水平均升高。由于胰岛中SOCS-3的转基因过表达使瘦素的脂肪减少作用降低了75%，我们得出结论，获得性肥胖大鼠WAT中SOCS-1和-3表达的增加可能阻断了瘦素在瘦素抵抗性WAT群体中的脂肪减少作用。
