Liraglutide pharmacotherapy reduces body weight and improves glycaemic control in juvenile obese/hyperglycaemic male and female rats

Diabetes Obes Metab. 2019 Apr;21(4):866-875. doi: 10.1111/dom.13591. Epub 2018 Dec 21.

Abstract

Aims: To examine whether the glucagon-like peptide-1 receptor agonist liraglutide could be used in juvenile male and female rats as an anti-obesity/diabetic pharmaceutical to prevent not only adolescent obesity/hyperglycaemia, but also early-adult onset obesity.

Material and methods: Pregnant dams were fed either standard chow or a high-fat, high-sucrose diet (HFSD) from gestational day 2, throughout pregnancy and lactation. Offspring were weaned onto the respective maternal diet. Juveniles received daily subcutaneous injection of liraglutide (50 μg/kg, from postnatal day [PND]30 to PND40 and 200 μg/kg from PND40 to PND60) or vehicle. Food intake, body weight and glycaemic levels were evaluated across the experimental period.

Results: Chronic liraglutide administration in juveniles prevented body weight gain in males and retained a normoglycaemic profile in both male and female rats.

Conclusion: These preclinical data suggest that maternal and early-life consumption of an HFSD increases caloric intake, body weight gain and hyperglycaemia, a collective set of unwanted metabolic effects that appear to be treatable in juveniles with liraglutide pharmacotherapy intervention.

Keywords: GLP-1 analogue; animal pharmacology; liraglutide; neuropharmacology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Body Weight / drug effects*
  • Diet, High-Fat
  • Dietary Sucrose
  • Eating / drug effects*
  • Female
  • Gestational Weight Gain
  • Hyperglycemia / metabolism*
  • Hypoglycemic Agents / pharmacology*
  • Liraglutide / pharmacology*
  • Male
  • Obesity / metabolism*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / metabolism
  • Rats

Substances

  • Blood Glucose
  • Dietary Sucrose
  • Hypoglycemic Agents
  • Liraglutide