Proulx Karine, Richard Denis, Walker Claire-Dominique
McGill University, Department of Psychiatry, Douglas Hospital Research Center, Montréal, Québec, Canada H4H 1R3.
Endocrinology. 2002 Dec;143(12):4683-92. doi: 10.1210/en.2002-220593.
Leptin regulates food intake in adult mammals by stimulating hypothalamic anorexigenic pathways and inhibiting orexigenic ones. In developing rodents, fat stores are low, yet circulating leptin levels are high and do not appear to regulate food intake. We determined whether two appetite-related neuropeptides [neuropeptide Y (NPY) and proopiomelanocortin (POMC)] and food intake behavior are sensitive to leptin [3 mg/kg body weight (BW), ip] in neonates. We measured the effects of 1) acute leptin administration (3 mg/kg BW, ip, 3 h before testing) on food intake on postnatal day (PND) 5, 8, and 10; and 2) chronic leptin treatment (3 mg/kg BW, ip, daily PND3-PND10) on BW gain and fat pads weight on PND10. In addition to hypothalamic POMC and NPY expression, we determined the expression of suppressor of cytokine signaling-3, all subtypes of leptin receptors, and corticotropin-releasing factor receptor-2 mRNA in PND10 pups receiving either an acute (PND10) or a chronic (PND 3-10) leptin (3 mg/kg BW, ip) or vehicle treatment. Brains were removed 30 or 120 min after the last injection. Acute leptin administration did not affect food intake at any age tested. Chronic leptin treatment did not change BW but decreased fat pad weight significantly. In the arcuate nucleus (ARC), acute leptin increased SOCS-3 and POMC mRNA levels, but decreased NPY mRNA levels in the rostral part of ARC. Chronic leptin down-regulated all subtypes of leptin receptors mRNA and decreased NPY mRNA levels in the caudal ARC but had no further effect on POMC expression. Chronic leptin increased corticotropin-releasing factor receptor-2 mRNA levels in the ventromedial hypothalamus. We conclude that despite adult-like effects of leptin on POMC, NPY, and CRFR-2 expression in neonates, leptin does not regulate food intake during early development.
瘦素通过刺激下丘脑厌食途径并抑制促食欲途径来调节成年哺乳动物的食物摄入。在发育中的啮齿动物中，脂肪储备较低，但循环瘦素水平较高，且似乎不调节食物摄入。我们确定了两种与食欲相关的神经肽[神经肽Y（NPY）和阿黑皮素原（POMC）]以及食物摄入行为对新生动物体内瘦素[3毫克/千克体重（BW），腹腔注射]是否敏感。我们测量了以下影响：1）急性给予瘦素（3毫克/千克BW，腹腔注射，测试前3小时）对出生后第5、8和10天的食物摄入量的影响；2）慢性瘦素治疗（3毫克/千克BW，腹腔注射，出生后第3天至第10天每天一次）对出生后第10天体重增加和脂肪垫重量的影响。除了下丘脑POMC和NPY的表达外，我们还确定了接受急性（出生后第10天）或慢性（出生后第3天至第10天）瘦素（3毫克/千克BW，腹腔注射）或溶剂处理的出生后第10天幼崽中细胞因子信号传导抑制因子-3、所有亚型的瘦素受体以及促肾上腺皮质激素释放因子受体-2 mRNA的表达。在最后一次注射后30或120分钟取出大脑。急性给予瘦素在任何测试年龄均未影响食物摄入量。慢性瘦素治疗未改变体重，但显著降低了脂肪垫重量。在弓状核（ARC）中，急性给予瘦素增加了细胞因子信号传导抑制因子-3和POMC mRNA水平，但降低了ARC前部的NPY mRNA水平。慢性瘦素下调了所有亚型的瘦素受体mRNA，并降低了ARC后部的NPY mRNA水平，但对POMC表达没有进一步影响。慢性瘦素增加了腹内侧下丘脑促肾上腺皮质激素释放因子受体-2 mRNA水平。我们得出结论，尽管瘦素对新生动物体内的POMC、NPY和CRFR-2表达具有类似成年动物的影响，但瘦素在早期发育过程中并不调节食物摄入。
