Intraventricular GLP-1 Reduces Short- But Not Long-Term Food Intake or Body Weight in Lean and Obese Rats

Brain Res. 1998 Jan 1;779(1-2):75-83. doi: 10.1016/s0006-8993(97)01057-3.

Abstract

Glucagon-like-peptide-1 (7-36) amide (GLP-1), when infused into the third ventricle (I.V.T.), reduces short-term food intake. In the present experiments, we assessed whether I.V.T. administration of GLP-1 could influence long-term food intake and body weight of lean Long Evans rats and of fatty Zucker (fa/fa) rats. In Experiment 1, we replicated the observation that 10 microg GLP-1, given I.V.T., reduces one and 2 h food intake, and extended the observation to fatty Zucker rats. However, in both rat strains, 24 h food intake and body weight were unchanged by this acute treatment. In Experiment 2, GLP-1 (30 microg/day) was infused I.V.T. continuously for 4 days via an osmotic mini-pump. This treatment also had no effect on food intake or body weight in either Long-Evans or fatty Zucker rats. A control experiment verified that the GLP-1 remained biologically active over the duration of the infusion period. In a final experiment, Long-Evans rats were restricted to two 2 h periods of access to food each day for 6 days. Prior to each of these access periods, rats received either 15 microg of GLP-1 I.V.T. or a vehicle control injection. While GLP-1 significantly reduced food intake on the first day of treatment, this effect of GLP-1 rapidly disappeared such that it was reduced on the second day and absent on the third day; and there was no effect on body weight at any time. Collectively, the present experiments do not support the hypothesis that GLP-1, acting in the CNS, is an important regulator of long-term food intake and body weight.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Body Weight / drug effects*
  • Cerebral Ventricles
  • Feeding Behavior / drug effects*
  • Glucagon / pharmacology*
  • Glucagon-Like Peptide 1
  • Infusion Pumps, Implantable
  • Male
  • Obesity / drug therapy*
  • Peptide Fragments / pharmacology*
  • Protein Precursors / pharmacology*
  • Rats
  • Rats, Zucker
  • Time Factors

Substances

  • Peptide Fragments
  • Protein Precursors
  • Glucagon-Like Peptide 1
  • Glucagon