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, IBAT temperature or fat pad weight. A peripheral injection of 2 mg leptin/kg on Day 23 or 26 inhibited energy intake of HS and NS, but not LiqS rats. Inhibition occurred earlier in HS than 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 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 that the pattern of sucrose consumption, rather than calories consumed as sucrose causes leptin resistance associated with site specific differences in hypothalamic leptin signaling.

中文翻译：

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消耗蔗糖溶液促进瘦素抵抗和位点特异性改变大鼠下丘脑瘦素信号传导

消耗 30% 蔗糖溶液和无蔗糖饮食 (LiqS) 的大鼠变得对瘦素有抵抗力，而从配方饮食 (HS) 中消耗蔗糖的大鼠仍然对瘦素有反应。这项研究测试了 LiqS 大鼠的瘦素抵抗是否超出了不能抑制食物摄入的范围，并检查了提供 HS、LiqS 或无蔗糖饮食 (NS) 的大鼠下丘脑和后脑中的瘦素反应。雌性 LiqS Sprague Dawley 大鼠最初仅部分补偿了作为蔗糖消耗的卡路里，但当它们被转移到量热笼时，能量摄入与 HS 和 NS 大鼠相匹配。饮食对能量消耗、IBAT 温度或脂肪垫重量没有影响。在第 23 天或第 26 天外周注射 2 mg 瘦素/kg 可抑制 HS 和 NS 的能量摄入，但不抑制 LiqS 大鼠的能量摄入。HS 比 NS 大鼠更早发生抑制，并且与较小的膳食大小有关。瘦素对能量消耗没有影响，但会导致 HS 大鼠的 IBAT 温度短暂升高。瘦素增加所有大鼠后脑和腹内侧下丘脑中的 pSTAT3。瘦素对弓状核的影响很小，只有背内侧下丘脑显示出 pSTAT3 和瘦素反应性之间的相关性。这些数据表明，对瘦素的主要反应是抑制食物摄入，并且蔗糖消耗的模式，而不是作为蔗糖消耗的卡路里导致瘦素抵抗与下丘脑瘦素信号的位点特异性差异相关。瘦素增加所有大鼠后脑和腹内侧下丘脑中的 pSTAT3。瘦素对弓状核的影响很小，只有背内侧下丘脑显示出 pSTAT3 和瘦素反应性之间的相关性。这些数据表明，对瘦素的主要反应是抑制食物摄入，并且蔗糖消耗的模式，而不是作为蔗糖消耗的卡路里导致瘦素抵抗与下丘脑瘦素信号的位点特异性差异相关。瘦素增加所有大鼠后脑和腹内侧下丘脑中的 pSTAT3。瘦素对弓状核的影响很小，只有背内侧下丘脑显示出 pSTAT3 和瘦素反应性之间的相关性。这些数据表明，对瘦素的主要反应是抑制食物摄入，并且蔗糖消耗的模式，而不是作为蔗糖消耗的卡路里导致瘦素抵抗与下丘脑瘦素信号的位点特异性差异相关。