Chavez M, Seeley R J, Havel P J, Friedman M I, Matson C A, Woods S C, Schwartz M W
Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104-3308, USA.
J Clin Invest. 1998 Jul 15;102(2):340-6. doi: 10.1172/JCI603.
Insulin-deficient diabetic rats are markedly hyperphagic when fed a high-carbohydrate (HC) diet, but normophagic when fed a high-fat (HF) diet. When maintained on a HC diet, diabetic rats also exhibit increased gene expression of the orexigenic peptide neuropeptide Y (NPY) in the hypothalamic arcuate nucleus, and reduced expression of the anorectic peptide corticotropin-releasing hormone (CRH) in the paraventricular nucleus, and these changes are hypothesized to contribute to diabetic hyperphagia. In this experiment we assessed whether the normophagia displayed by HF-fed diabetic rats is associated with the opposite profile of NPY and CRH expression. Our results show that relative to diabetic rats on the HC diet, the diabetic rats on the HF diet exhibited significantly reduced caloric intake (-40%), NPY expression in the arcuate nucleus (-27%), and elevated CRH expression in the paraventricular nucleus (+37%). Insulin and corticosterone, which are known to affect hypothalamic NPY and CRH expression, were not different between these two groups, making it unlikely that they can account for the differences in either feeding behavior or hypothalamic peptide expression. There was a small but significant increase in plasma leptin levels in the diabetic animals maintained on the HF, and large differences in parameters associated with elevated fat oxidation. These observations support the hypothesis that the normalization of food intake observed in diabetic rats consuming a HF diet may in part be mediated by reductions in NPY expression and elevations in CRH expression.
胰岛素缺乏的糖尿病大鼠在喂食高碳水化合物（HC）饮食时会明显食欲亢进，但在喂食高脂肪（HF）饮食时则食欲正常。当维持HC饮食时，糖尿病大鼠下丘脑弓状核中促食欲肽神经肽Y（NPY）的基因表达也会增加，而室旁核中促食欲肽促肾上腺皮质激素释放激素（CRH）的表达则会减少，这些变化被认为与糖尿病性多食有关。在本实验中，我们评估了喂食HF的糖尿病大鼠表现出的正常食欲是否与NPY和CRH表达的相反情况有关。我们的结果表明，与喂食HC饮食的糖尿病大鼠相比，喂食HF饮食的糖尿病大鼠的热量摄入显著减少（-40%），弓状核中的NPY表达减少（-27%），而室旁核中的CRH表达升高（+37%）。已知会影响下丘脑NPY和CRH表达的胰岛素和皮质酮在这两组之间没有差异，因此它们不太可能解释进食行为或下丘脑肽表达的差异。喂食HF的糖尿病动物的血浆瘦素水平有小幅但显著的升高，并且与脂肪氧化增加相关的参数存在很大差异。这些观察结果支持了这样一种假设，即食用HF饮食的糖尿病大鼠中观察到的食物摄入量正常化可能部分是由NPY表达的减少和CRH表达的升高介导的。
