血浆瘦素、胰岛素和游离色氨酸导致细胞因子诱导的厌食症。

Plasma leptin, insulin and free tryptophan contribute to cytokine-induced anorexia.

作者信息

Sato Tomoi, Laviano Alessandro, Meguid Michael M, Rossi-Fanelli Filippo

机构信息

Surgical Metabolism and Nutrition Laboratory, Department of Surgery, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA.

出版信息

Adv Exp Med Biol. 2003;527:233-9. doi: 10.1007/978-1-4615-0135-0_27.

DOI:10.1007/978-1-4615-0135-0_27

PMID:15206737

Abstract

Cytokines contribute to anorexia of diseases. Tumor Necrosis Factor (TNF) and/or interleukin-1 (IL-1) stimulate leptin release, but not insulin. Both affect hypothalamus to decrease food intake (FI). Hypothalamic serotonin (5HT) decreases FI. Its synthesis depends on brain availability of precursor, tryptophan (TRP), which depends on plasma free TRP. Purpose is to test involvement of plasma leptin, insulin, TRP, and thus hypothalamic 5HT in cytokine-induced anorexia in rats. In male rats, IL-1alpha (10 mg/kg/d; n=9), TNFalpha (30 mg/kg/d; n=9), Il-1alpha+TNFalpha (10:30 mg/kg/d; n=9), TRP (100 mg/kg/d, n=8) and saline (n=8; Control) were injected sc for 2 days. FI, BW, plasma free and total TRP, leptin and insulin, and body fat were measured. Data analyzed via ANOVA. IL-1alpha and IL-1alpha+TNFalpha vs others decreased FI and BW. TNFalpha and TRP did not change FI and BW. Plasma total TRP was higher in TRP vs IL-1alpha, TNFalpha, and IL-1alpha+TNFalpha. Plasma free TRP was higher in IL-1alpha and IL-1alpha+TNFalpha vs Control. IL-1alpha and IL-1alpha+TNFalpha decreased leptin and body fat. Insulin in Control was lower than others. Data suggest: i) IL-1alpha increases plasma free TRP, but not total TRP, thus increases hypothalamic 5HT synthesis, resulting in anorexia; ii) leptin does not mediate anorexia, but; iii) insulin may contribute to anorexia induced by cytokines.

摘要

细胞因子导致疾病性厌食。肿瘤坏死因子（TNF）和/或白细胞介素-1（IL-1）刺激瘦素释放，但不刺激胰岛素释放。二者均作用于下丘脑以减少食物摄入量（FI）。下丘脑5-羟色胺（5HT）减少食物摄入量。其合成取决于前体色氨酸（TRP）在脑内的可利用性，而这又取决于血浆游离TRP。目的是检测血浆瘦素、胰岛素、TRP以及下丘脑5HT在细胞因子诱导的大鼠厌食中的作用。对雄性大鼠皮下注射IL-1α（10mg/kg/d；n=9）、TNFα（30mg/kg/d；n=9）、IL-1α+TNFα（10:30mg/kg/d；n=9）、TRP（100mg/kg/d，n=8）和生理盐水（n=8；对照），持续2天。测量食物摄入量、体重、血浆游离和总TRP、瘦素和胰岛素以及体脂。数据通过方差分析进行分析。与其他组相比，IL-1α和IL-1α+TNFα降低了食物摄入量和体重。TNFα和TRP未改变食物摄入量和体重。与IL-1α、TNFα和IL-1α+TNFα相比，TRP组的血浆总TRP更高。与对照组相比，IL-1α和IL-1α+TNFα组的血浆游离TRP更高。IL-1α和IL-1α+TNFα降低了瘦素和体脂。对照组的胰岛素低于其他组。数据表明：i）IL-1α增加血浆游离TRP，但不增加总TRP，从而增加下丘脑5HT合成，导致厌食；ii）瘦素不介导厌食，但；iii）胰岛素可能促成细胞因子诱导的厌食。