Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 386, Issue 8, pp 721–732

Effects of CB1 receptor blockade on monosodium glutamate induced hypometabolic and hypothalamic obesity in rats

  • Wei Chen
  • Zhenhua Chen
  • Nina Xue
  • Zhibing Zheng
  • Song Li
  • LiLi Wang
Original Article

DOI: 10.1007/s00210-013-0875-y

Cite this article as:
Chen, W., Chen, Z., Xue, N. et al. Naunyn-Schmiedeberg's Arch Pharmacol (2013) 386: 721. doi:10.1007/s00210-013-0875-y

Abstract

Effects of cannabinoid receptor 1 (CB1R) blockade were observed by comparing 9-day and 6-week SR141716 treatments in monosodium glutamate (MSG)-induced hypometabolic and hypothalamic obesity (HO) in rats for the first time and molecular mechanisms were investigated. Compared with normal rats, the MSG rats display typical symptoms of the metabolic syndrome, i.e., excessive abdominal obesity, hypertriglyceridemia, hyperinsulinemia, insulin resistance, and hepatic steatosis, but with lower food intake. Although both the 9-day and 6-week treatments with the specific CB1R antagonist SR141716 effectively lowered body weight, intraperitoneal adipose tissue mass, serum triglyceride (TG), and insulin level, the effect of chronic treatment is more impressive. Moreover, serum cholesterol, free fatty acids (FFA), fasted and postprandial blood glucose, and insulin insensitivity were more effectively improved by 6-week exposure to SR141716, whereas hypophagia was only effective within the initial 2 weeks. In addition, hepatic steatosis as well as hepatic and adipocyte morphology was improved. Western blot analysis revealed that the markedly increased CB1R expression and decreased insulin receptor (INR) expression in liver and adipose tissues were effectively corrected by SR141716. Consistent with this, deregulated gene expression of lipogenesis and lipolysis as well as glucose metabolic key enzymes were also restored by SR141716. In conclusion, based on present data we found that: (1) alteration of the hypothalamus in MSG rats leads to a lower expression of INR in crucially insulin-targeted tissues and hyperinsulinemia that was reversed by SR141716, (2) the abnormally increased expression of CB1R in liver and adipose tissues plays a vital role in the pathophysiological process of MSG rats, and (3) chronic CB1R blockade leads to a sustained improvement of the metabolic dysfunctions of MSG rats.

Keywords

CB1 receptor Hypometabolic obesity Hypothalamic obesity Insulin sensitivity Antagonist 

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Wei Chen
    • 1
  • Zhenhua Chen
    • 1
  • Nina Xue
    • 1
  • Zhibing Zheng
    • 1
  • Song Li
    • 1
  • LiLi Wang
    • 1
  1. 1.Beijing Institute of Pharmacology and ToxicologyBeijingChina

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