Hypothalamic pro-opiomelanocortin mRNA is reduced by fasting in ob/ob and db/db mice, but is stimulated by leptin
Hypothalamic pro-opiomelanocortin mRNA is reduced by fasting in ob/ob and db/db mice, but is stimulated by leptin
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DOI：
10.2337/diabetes.47.2.294
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发表时间：
1998-02-01
期刊：
影响因子：
7.7
通讯作者：
Mobbs, CV
中科院分区：
文献类型：
--
作者：
Mizuno, TM;Kleopoulos, SP;Mobbs, CV
α-黑素细胞刺激素(α-MSH)系统活性降低会导致肥胖，注射α-MSH会产生饱腹感，增加了α-MSH可能介导生理饱腹感信号的可能性，因为α-MSH是由前阿片黑素皮质素(POMC)基因编码的，PIE检查正常小鼠或以瘦素不足(ob/ob)或瘦素不敏感(db/db)为特征的肥胖模型中POMC基因的表达是否会被抑制。在野生型小鼠中，禁食2天后下丘脑POMC信使核糖核酸减少60%，且与瘦素信使核糖核酸呈正相关。与对照组相比，db/db和ob/ob小鼠POMC信使核糖核酸至少降低60%，POMC信使核糖核酸与神经肽Y(NPY)和黑色素浓缩激素(MCH)信使核糖核酸呈负相关，雌雄均可刺激下丘脑POCM信使核糖核酸增加约3倍。这些结果提示，肥胖小鼠的生产、加工或对α-MSH的反应性受损可能是肥胖的共同特征，瘦素刺激的下丘脑POMC神经元可能是瘦素和黑素皮质素系统之间的联系。
Reduction in the activity of the alpha-melanocyte-stimulating hormone (alpha-MSH) system causes obesity and infusions of alpha-MSH call produce satiety, raising the possibility that alpha-MSH may mediate physiological satiety signals, Since alpha-MSH is coded for by the pro-opiomelanocortin (POMC) gene, pie examined if POMC gene expression would be inhibited by fasting in normal mice or in models of obesity characterized by leptin insufficiency (ob/ob) or leptin insensitivity (db/db). in wild-type mice, hypothalamic POMC mRNA was decreased >60% after a 2-day fast and was positively correlated with leptin mRNA. Similarly compared with controls, POMC mRNA was decreased by at least 60% in both db/db and ob/ob mice, POMC mRNA was negatively correlated with both neuropeptide Y (NPY) and melanin-concentrating hormone (MCH) mRNA, Finally, treatment of both male and female ob/ob mice with leptin stimulated hypothalamic POCM mRNA by about threefold, These results suggest that impairment in production, processing, or responsiveness to alpha-MSH may be a common feature of obesity and that hypothalamic POMC neurons, stimulated by leptin, may constitute a Link between leptin and the melanocortin system.