胃旁路术后体重减轻相关的下丘脑神经生物学变化。

Neurobiologic changes in the hypothalamus associated with weight loss after gastric bypass.

作者信息

Romanova Irina V, Ramos Eduardo J B, Xu Yuan, Quinn Robert, Chen Chung, George Zachariah M, Inui Akio, Das Undurti, Meguid Michael M

机构信息

Surgical Metabolism and Nutrition Laboratory, Neuroscience Program, Department of Surgery, University Hospital, SUNY Upstate Medical University, Syracuse, NY, USA.

出版信息

J Am Coll Surg. 2004 Dec;199(6):887-95. doi: 10.1016/j.jamcollsurg.2004.07.013.

DOI:10.1016/j.jamcollsurg.2004.07.013

PMID:15555972

Abstract

BACKGROUND

Effects of Roux-en-Y gastric bypass (RYGB) on hypothalamic food intake regulation have not been investigated. The hypothalamic arcuate nucleus (ARC) and the magnocellular (m) and parvocellular (p) parts of the paraventricular nucleus (PVN) regulate hunger and satiety, and are under control of the orexigenic neuropeptide Y (NPY), and the anorexigenic alpha-melanocyte stimulating hormone (alpha-MSH) and serotonin (5-HT). We hypothesized that after RYGB, weight loss is associated with hypothalamic down regulation of NPY and up regulation of 5-HT and alpha-MSH.

STUDY DESIGN

Obesity was induced in 12 Sprague Dawley rats using a high-energy diet for 7 weeks, and then the rats were divided into three groups (n = 4/group): RYGB, sham-operated pair-fed (PF), and sham-operated ad libitum (obese control). Ten days after operation, immunohistochemical quantification of NPY, alpha-MSH, and 5-HT(1B)-receptors in ARC and PVN was performed. Data were analyzed using ANOVA and Tukey's test.

RESULTS

Body weight decreased in RYGB (417 +/- 21 g; mean +/- SE) and in PF (436 +/- 14 g) rats 10 days after operation compared with obese control rats (484 +/- 15 g; p < 0.05 for each comparison). NPY in ARC, pPVN, and mPVN decreased by 43%, 43%, and 61%, respectively in RYGB and by 55%, 42%, and 71% in PF, respectively, compared with obese controls (p < 0.05 for each pairwise comparison). RYGB versus PF did not show differences. alpha-MSH in ARC, pPVN and mPVN increased by 35%, 175%, and 67%, respectively in RYGB and by 29%, 162%, and 116% in PF, respectively, compared with obese controls (each p < 0.05). In mPVN, alpha-MSH significantly decreased by 23% in RYGB versus PF (p < 0.05). 5-HT-(1B)-receptor in pPVN increased by 58% in RYGB and by 26% in PF, compared with obese controls (p < 0.05). Compared with obese controls, 5HT-(1B)-receptor in mPVN increased by 39% in RYGB (p < 0.05) and by 9% in PF (p > 0.05). An increase of 5-HT-(1B)-receptor in pPVN and mPVN occurred in RYGB versus PF (p < 0.05).

CONCLUSIONS

Obese rats that undergo weight loss after RYGB demonstrate changes in hypothalamic down regulation of NPY and up regulation of alpha-MSH and serotonin.

摘要

背景

Roux-en-Y胃旁路术（RYGB）对下丘脑食物摄入调节的影响尚未得到研究。下丘脑弓状核（ARC）以及室旁核（PVN）的大细胞（m）和小细胞（p）部分调节饥饿和饱腹感，并且受促食欲神经肽Y（NPY）、抑食欲α-黑素细胞刺激激素（α-MSH）和5-羟色胺（5-HT）的控制。我们假设RYGB术后体重减轻与下丘脑NPY下调以及5-HT和α-MSH上调有关。

研究设计

使用高能饮食7周诱导12只Sprague Dawley大鼠肥胖，然后将大鼠分为三组（每组n = 4）：RYGB组、假手术配对喂养（PF）组和假手术自由进食（肥胖对照）组。术后10天，对ARC和PVN中的NPY、α-MSH和5-HT（1B）受体进行免疫组化定量分析。数据采用方差分析和Tukey检验进行分析。

结果

与肥胖对照大鼠（484±15 g）相比，RYGB组（417±21 g；均值±标准误）和PF组大鼠术后10天体重下降（每组比较p < 0.05）。与肥胖对照相比，RYGB组ARC、pPVN和mPVN中的NPY分别下降43%、43%和61%，PF组分别下降55%、42%和71%（每组两两比较p < 0.05）。RYGB组与PF组之间未显示出差异。与肥胖对照相比，RYGB组ARC、pPVN和mPVN中的α-MSH分别增加35%、175%和67%，PF组分别增加29%、162%和116%（各p < 0.05）。在mPVN中，RYGB组与PF组相比α-MSH显著下降23%（p < 0.05）。与肥胖对照相比，RYGB组pPVN中的5-HT-（1B）受体增加58%，PF组增加26%（p < 0.05）。与肥胖对照相比，RYGB组mPVN中的5HT-（1B）受体增加39%（p < 0.05），PF组增加9%（p > 0.05）。RYGB组与PF组相比，pPVN和mPVN中的5-HT-（1B）受体增加（p < 0.05）。