Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters - A role for leptin in the anorexia of infection

Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters - A role for leptin in the anorexia of infection
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DOI:
10.1172/jci118653
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发表时间:
1996-05-01
影响因子:
15.9
通讯作者:
Feingold, KR
Feingold, KR
中科院分区:
医学1区
文献类型:
--
作者:
Grunfeld, C;Zhao, C;Feingold, KR

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由于脂肪组织基因表达受感染时诱导的细胞因子调控,并且感染与厌食症相关,因此我们测试了在宿主对感染的反应中是否会诱导瘦素的产生。在禁食动物中,脂多糖使脂肪组织中瘦素mRNA的表达增加到与喂食对照动物相似的水平,瘦素mRNA水平与随后的食物摄入量呈强烈的负相关,宿主对脂多糖反应的介质TNF和IL-1也诱导了厌食和脂肪组织中瘦素mRNA水平的增加。免疫沉淀和Western blotting检测表明,脂多糖和细胞因子在调控脂肪组织瘦素mRNA的同时调控循环瘦素蛋白,宿主对感染反应过程中瘦素的诱导可能导致感染厌食。
The expression of leptin, the ob gene product, is increased in adipose tissue in response to feeding and energy repletion, while leptin expression decreases during fasting, Infusion of leptin decreases food intake, Because adipose tissue gene expression is regulated by cytokines induced during infection and because infection is associated with anorexia, we tested whether induction of leptin might occur during the host response to infection, Administration of endotoxin (LPS), a model for gram negative infections, induces profound anorexia and weight loss in hamsters, In fasted animals, LPS increased the expression of leptin mRNA in adipose tissue to levels similar to fed control animals, There is a strong inverse correlation between mRNA levels of leptin and subsequent food intake, TNF and IL-1, mediators of the host response to LPS, also induced anorexia and increased levels of leptin mRNA in adipose tissue. As assessed by immunoprecipitation and Western blotting, circulating leptin protein is regulated by LPS and cytokines in parallel to regulation of adipose tissue leptin mRNA, Induction of leptin during the host response to infection may contribute to the anorexia of infection.