Glucagon-like peptide-1(9-36)amide metabolite inhibits weight gain and attenuates diabetes and hepatic steatosis in diet-induced obese mice

Diabetes Obes Metab. 2011 Jan;13(1):26-33. doi: 10.1111/j.1463-1326.2010.01316.x.

Abstract

Aims: The metabolic syndrome, a disease arising from the world-wide epidemic of obesity, is manifested as severe insulin resistance, hyperlipidaemia, hepatic steatosis and diabetes. Previously we reported that GLP-1(9-36)amide, derived from the gluco-incretin hormone, glucagon-like peptide-1 (GLP-1), suppresses gluconeogenesis in isolated hepatocytes. The aims of this study were to determine the effects of GLP-1(9-36)amide in diet-induced obese mice that model the development of the metabolic syndrome.

Methods: Mice rendered obese by feeding a very high fat diet were administered GLP-1(9-36)amide via subcutaneous osmopumps for 8 weeks. Body weight, energy intake, plasma insulin and glucose levels (insulin-resistance), and hepatic steatosis were assessed.

Results: Eight-week infusions of GLP-1(9-36)amide inhibited weight gain, increased energy intake, prevented the development of fasting hyperinsulinaemia and hyperglycaemia, and curtailed the accumulation of liver triglycerides. The peptide had no effects in mice fed a normal chow diet. Notably, energy intake in the obese mice receiving GLP-1(9-36)amide was 20% greater than obese mice receiving vehicle control.

Conclusions: GLP-1(9-36)amide exerts insulin-like actions in the presence of insulin resistance and prevents the development of metabolic syndrome. Curtailment of weight gain in the face of increased caloric intake suggests that GLP-1(9-36)amide increases energy expenditure. These findings suggest the possibility of the use of GLP-1(9-36)amide, or a peptide mimetic derived there from, for the treatment of obesity, insulin resistance and the metabolic syndrome.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Dietary Fats / administration & dosage
  • Energy Intake
  • Fatty Liver / metabolism*
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucagon-Like Peptide 1 / pharmacology
  • Insulin / biosynthesis
  • Male
  • Metabolic Syndrome / drug therapy
  • Metabolic Syndrome / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Receptors, Glucagon / metabolism*
  • Weight Gain / drug effects*

Substances

  • Dietary Fats
  • Insulin
  • Receptors, Glucagon
  • Glucagon-Like Peptide 1