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Phosphorylation of STAT3 in hypothalamic nuclei is stimulated by lower doses of leptin than are needed to inhibit food intake
American Journal of Physiology-Endocrinology and Metabolism ( IF 5.1 ) Pub Date : 2021-06-14 , DOI: 10.1152/ajpendo.00143.2021
Ruth B S Harris 1
Affiliation  

This experiment investigated which hypothalamic nuclei were activated by a dose of leptin that inhibited food intake. Food intake, energy expenditure, respiratory exchange ratio (RER) and intrascapular brown adipose tissue (IBAT) temperature were measured in male and female Sprague Dawley rats for 36 hours following an intraperitoneal injection of 0, 50, 200, 500 or 1000 mg leptin/kg with each rat tested with each dose of leptin in random order. In both males and females RER and 12 hour food intake and were inhibited only by 1000 mg leptin/kg, but there was no effect on energy expenditure or IBAT temperature. At the end of the experiment pSTAT3 immunoreactivity was measured one hour after injection of 0, 50, 500 or 1000 mg leptin/kg. In male rats the lowest dose of leptin produced a maximal activation of STAT3 in the Arc and nucleus of the solitary tract (NTS). There was no response in the dorsomedial hypothalamus but there was a progressive increase in VMH pSTAT3 with increasing doses of leptin. In female rats there was no significant change in Arc pSTAT3, NTS activation was maximal with 500 mg leptin/kg, but only the highest dose of leptin increased VMH pSTAT3. These results suggest that the VMH plays an important role in the energetic response to elevations of circulating leptin, but do not exclude the possibility that multiple nuclei provide the appropriate integrated response to hyperleptinemia.

中文翻译:

低于抑制食物摄入所需的瘦素剂量可刺激下丘脑核中 STAT3 的磷酸化

该实验研究了抑制食物摄入的瘦素剂量激活了哪些下丘脑核。在腹膜内注射 0、50、200、500 或 1000 mg 瘦素后 36 小时,测量雄性和雌性 Sprague Dawley 大鼠的食物摄入量、能量消耗、呼吸交换比 (RER) 和肩胛内棕色脂肪组织 (IBAT) 温度/每只大鼠以随机顺序用每种剂量的瘦素进行测试。在男性和女性的 RER 和 12 小时食物摄入中,仅受到 1000 mg 瘦素/kg 的抑制,但对能量消耗或 IBAT 温度没有影响。在实验结束时,在注射 0、50、500 或 1000 mg 瘦素/kg 后一小时测量 pSTAT3 免疫反应性。在雄性大鼠中,最低剂量的瘦素在孤束 (NTS) 的弧和核中产生最大的 STAT3 激活。下丘脑背内侧没有反应,但随着瘦素剂量的增加,VMH pSTAT3 逐渐增加。在雌性大鼠中,Arc pSTAT3 没有显着变化,NTS 激活在 500 mg leptin/kg 时最大,但只有最高剂量的 leptin 增加 VMH pSTAT3。这些结果表明 VMH 在对循环瘦素升高的能量反应中起重要作用,但不排除多核对高瘦素血症提供适当的综合反应的可能性。在雌性大鼠中,Arc pSTAT3 没有显着变化,NTS 激活在 500 mg leptin/kg 时最大,但只有最高剂量的 leptin 增加 VMH pSTAT3。这些结果表明 VMH 在对循环瘦素升高的能量反应中起重要作用,但不排除多核对高瘦素血症提供适当的综合反应的可能性。在雌性大鼠中,Arc pSTAT3 没有显着变化,NTS 激活在 500 mg leptin/kg 时最大,但只有最高剂量的 leptin 增加 VMH pSTAT3。这些结果表明 VMH 在对循环瘦素升高的能量反应中起重要作用,但不排除多核对高瘦素血症提供适当的综合反应的可能性。
更新日期:2021-06-15
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