Department of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia.
Am J Physiol Regul Integr Comp Physiol. 2021 Feb 1;320(2):R182-R194. doi: 10.1152/ajpregu.00238.2020. Epub 2020 Nov 18.
Rats consuming 30% sucrose solution and a sucrose-free diet (LiqS) become leptin resistant, whereas rats consuming sucrose from a formulated diet (HS) remain leptin responsive. This study tested whether leptin resistance in LiqS rats extended beyond a failure to inhibit food intake and examined leptin responsiveness in the hypothalamus and hindbrain of rats offered HS, LiqS, or a sucrose-free diet (NS). Female LiqS Sprague-Dawley rats initially only partially compensated for the calories consumed as sucrose, but energy intake matched that of HS and NS rats when they were transferred to calorimetry cages. There was no effect of diet on energy expenditure, intrascapular brown fat tissue (IBAT) temperature, or fat pad weight. A peripheral injection of 2 mg of leptin/kg on or inhibited energy intake of HS and NS but not LiqS rats. Inhibition occurred earlier in HS rats than in NS rats and was associated with a smaller meal size. Leptin had no effect on energy expenditure but caused a transient rise in IBAT temperature of HS rats. Leptin increased the phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) in the hindbrain and ventromedial hypothalamus of all rats. There was a minimal effect of leptin in the arcuate nucleus, and only the dorsomedial hypothalamus showed a correlation between pSTAT3 and leptin responsiveness. These data suggest that the primary response to leptin is inhibition of food intake and the pattern of sucrose consumption, rather than calories consumed as sucrose, causes leptin resistance associated with site-specific differences in hypothalamic leptin signaling.
食用 30%蔗糖溶液和无糖饮食（LiqS）的大鼠会对瘦素产生抗性，而食用配方饮食中蔗糖（HS）的大鼠仍对瘦素有反应。本研究测试了 LiqS 大鼠的瘦素抵抗是否超出了抑制食物摄入的失败范围，并检查了提供 HS、LiqS 或无糖饮食（NS）的大鼠下丘脑和后脑的瘦素反应。最初，LiqS Sprague-Dawley 雌性大鼠仅部分补偿了作为蔗糖消耗的卡路里，但当它们转移到热量计笼中时，能量摄入量与 HS 和 NS 大鼠相匹配。饮食对能量消耗、肩胛间棕色脂肪组织（IBAT）温度或脂肪垫重量没有影响。在第 或第 天，给 2 mg/kg 的外周注射瘦素抑制了 HS 和 NS 大鼠的能量摄入，但不抑制 LiqS 大鼠的能量摄入。抑制作用在 HS 大鼠中比在 NS 大鼠中更早发生，并且与较小的餐量有关。瘦素对能量消耗没有影响，但导致 HS 大鼠的 IBAT 温度短暂升高。瘦素增加了所有大鼠后脑和下丘脑腹内侧核中信号转导和转录激活因子 3（pSTAT3）的磷酸化。瘦素对弓状核的影响最小，只有下丘脑背内侧核显示 pSTAT3 与瘦素反应性之间存在相关性。这些数据表明，对瘦素的主要反应是抑制食物摄入，而蔗糖的消耗模式而不是作为蔗糖消耗的卡路里，导致与下丘脑瘦素信号的特定部位差异相关的瘦素抵抗。
