Glucagon-like peptide-1 agonist exendin-4 leads to reduction of weight and caloric intake in a rat model of hypothalamic obesity

Horm Res Paediatr. 2012;78(1):47-53. doi: 10.1159/000338464. Epub 2012 Jul 20.

Abstract

Background: Hypothalamic obesity caused by damage of medial hypothalamic nuclei presents a therapeutic challenge. Glucagon-like peptide-1 agonist exenatide (synthetic version of exendin-4 (Ex4)), used for treatment of diabetes, causes weight loss via hindbrain signaling.

Methods: We tested Ex4 in an established rat model of medial hypothalamic lesions. Lesion and control animals were administered either daily intraperitoneal injections of 1 µg·kg(-1) Ex4 or saline for 9 days.

Results: In our rat model, a significant difference in percent baseline food intake (lesion -20.8%, control -13.6%; p < 0.001) and percent change in body weight (lesion -4.9%/9 days, control -3.2%/9 days; p < 0.05) was observed during Ex4 treatment compared with saline.

Conclusion: Ex4 resulted in reduction of food intake and body weight. Follow-up studies are required to further elucidate its effects on energy homeostasis and to establish Ex4 as a potential drug for treatment of hypothalamic obesity.

MeSH terms

  • Animals
  • Body Weight / drug effects*
  • Body Weight / physiology
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Drug Evaluation, Preclinical
  • Energy Intake / drug effects*
  • Energy Intake / physiology
  • Exenatide
  • Glucagon-Like Peptide 1 / agonists
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Hypothalamic Diseases / complications
  • Hypothalamic Diseases / drug therapy
  • Hypothalamic Diseases / metabolism
  • Hypothalamic Diseases / pathology
  • Male
  • Obesity / drug therapy*
  • Obesity / etiology
  • Obesity / metabolism
  • Obesity / pathology
  • Peptides / pharmacology*
  • Peptides / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Venoms / pharmacology*
  • Venoms / therapeutic use
  • Weight Loss / drug effects
  • Weight Loss / physiology

Substances

  • Hypoglycemic Agents
  • Peptides
  • Venoms
  • Glucagon-Like Peptide 1
  • Exenatide