Hypothalamic pathways regulate the anorectic action of p-chloro-diphenyl diselenide in rats

Eur J Pharmacol. 2017 Nov 15;815:241-250. doi: 10.1016/j.ejphar.2017.09.032. Epub 2017 Sep 21.

Abstract

Behavioral studies have suggested that (p-ClPhSe)2 elicits an anorectic-like action in rats by inducing multiple effects such as satiety-enhancing effect, malaise and specific flavor; however, the molecular mechanisms underlying its anorexigenic action remain unclarified. Here, male Sprague-Dawley rats received acute and sub-chronic intraperitoneal treatments with (p-ClPhSe)2; thereafter, in vivo and ex vivo analyses were carried out. The present study reveals that the reduction of food intake resulting from a single treatment with (p-ClPhSe)2 (1mg/kg, i.p.) was associated with decreased hypothalamic levels of pro-melanin-concentrating hormone (pro-MCH) and orexin precursor. In addition, repeated administrations of (p-ClPhSe)2 (10mg/kg; i.p.) for 7 days induced sustained food intake suppression, body weight loss and white fat reduction. Measurements of brown adipose tissue content and temperature as well as data obtained from a pair-fed group indicated that the effects of (p-ClPhSe)2 on the body weight are closely related to its anorexigenic actions, ruling out the possibility of increased thermogenesis. Furthermore, (p-ClPhSe)2 reduced the hypothalamic orexin precursor levels when repeatedly administered to rats. Sub-chronic treatment with (p-ClPhSe)2 caused a decrease of serum triglyceride levels and down-regulation of hepatic cholesterol content. Therefore, the current study characterized the anorectic and reducing body weight actions of (p-ClPhSe)2 in Sprague-Dawley rats. Besides, the set of results suggests that food intake suppressant effects triggered after (p-ClPhSe)2 administration to rats are mainly related with the lower orexin levels in hypothalamus after acute and sub-chronic treatments.

Keywords: Appetite suppressant; Body weight loss; Neuropeptides; Orexin; Selenium.

MeSH terms

  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism
  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / metabolism
  • Animals
  • Anorexia / blood
  • Anorexia / chemically induced*
  • Anorexia / pathology*
  • Anorexia / psychology
  • Body Composition / drug effects
  • Body Weight / drug effects
  • Eating / drug effects
  • Hypothalamus / drug effects*
  • Hypothalamus / metabolism
  • Hypothalamus / pathology*
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Organoselenium Compounds / adverse effects*
  • Rats
  • Rats, Sprague-Dawley
  • Satiety Response / drug effects
  • Time Factors
  • Triglycerides / blood

Substances

  • Organoselenium Compounds
  • Triglycerides
  • p-chloro-diphenyl diselenide