Leptin rapidly lowers food intake and elevates metabolic rates in lean and ob/ob mice.
Leptin rapidly lowers food intake and elevates metabolic rates in lean and ob/ob mice.
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DOI：
10.1093/jn/127.10.2065
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发表时间：
1997-10
期刊：
影响因子：
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通讯作者：
A. Mistry;Swick Andrew Gordon;D. Romsos
中科院分区：
文献类型：
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作者：
A. Mistry;Swick Andrew Gordon;D. Romsos
瘦素是ob基因的产物，从脂肪组织中释放出来，可能作用于中枢神经系统，特别是下丘脑，发挥其许多作用。C57 BL/6 J ob/ob小鼠的肥胖是由ob基因突变引起的，导致功能性瘦素缺乏。在这项研究中，我们首先比较了单次脑室内（ICV）注射3 pmol（50 ng）或60 pmol（1 μ g）瘦素对瘦和ob/ob小鼠的摄食量和耗氧量的影响，在注射后48小时内剥夺食物4小时。注射3 pmol瘦素最低限度地降低了这些小鼠的摄食量，而不影响耗氧量。注射60 pmol的瘦素在30 min内迅速降低瘦小鼠和肥胖/肥胖小鼠的摄食量，其作用持续24 h。瘦和ob/ob小鼠瘦素治疗消耗的食物，分别减少40和60%，在24小时内比车辆处理的控制。注射瘦素（60 pmol ICV）抑制肾上腺切除小鼠的摄食量（瘦小鼠在3和24 h分别为25%和40%，ob/ob小鼠分别为20%和68%），表明糖皮质激素不是瘦素抑制摄食量所必需的。瘦素在饮食诱导的产热低的条件下增加耗氧量，即，在进食的ob/ob小鼠和食物剥夺的瘦型小鼠中，但在进食的肾上腺切除的ob/ob小鼠或进食的瘦型小鼠中没有。ICV注射60 pmol瘦素沿着230 pmol（2 μ g）神经肽Y（NPY）减弱了ob/ob小鼠的NPY诱导的进食，但在瘦小鼠中没有，这表明缺乏内源性瘦素的ob/ob小鼠中瘦素和NPY信号系统之间的串扰的可能性增强。瘦素在中枢神经系统内发挥快速作用，以协调控制食物摄入和代谢率。
Leptin, the ob gene product, is released from adipose tissue and likely acts in the central nervous system, particularly within the hypothalamus, to exert many of its effects. Obesity in C57BL/6J ob/ob mice is caused by a mutation in the ob gene resulting in a lack of functional leptin. In this study, we first compared effects of a single intracerebroventricular (ICV) injection of 3 pmol (50 ng) or 60 pmol (1 microg) leptin on food intake and oxygen consumption of lean and ob/ob mice deprived of food for 4 h during the 48-h period postinjection. Injection of 3 pmol leptin minimally lowered food intake in these mice without influencing oxygen consumption. Injection of 60 pmol of leptin rapidly lowered food intake within 30 min in both lean and ob/ob mice, with effects persisting for 24 h. Lean and ob/ob mice treated with leptin consumed 40 and 60% less food, respectively, in 24 h than vehicle-treated controls. Injection of leptin (60 pmol ICV) suppressed food intake of adrenalectomized mice as well (by 25 and 40% in lean mice and by 20 and 68% in ob/ob mice at 3 and 24 h, respectively), indicating that glucocorticoids are not essential for leptin to suppress food intake. Leptin increased oxygen consumption in conditions in which diet-induced thermogenesis was low, i.e., in fed ob/ob mice and in food-deprived lean mice, but not in fed adrenalectomized ob/ob mice or in fed lean mice. ICV injection of 60 pmol leptin along with 230 pmol (2 microg) of neuropeptide Y (NPY) attenuated NPY-induced feeding in ob/ob, but not in lean mice, suggesting an enhanced potential for crosstalk between the leptin and NPY signaling systems in ob/ob mice lacking endogenous leptin. Leptin exerts rapid-onset actions within the central nervous system to coordinate control of food intake and metabolic rate.