Advanced onset of puberty after metformin therapy in swine with thrifty genotype

Exp Physiol. 2014 Sep;99(9):1241-52. doi: 10.1113/expphysiol.2014.081455. Epub 2014 Aug 1.

Abstract

The prevention and treatment of obesity in children is based on adequate nutrition and exercise plus antihyperglycaemic drugs. Currently, the incidence of childhood obesity is aggravated in ethnicities with thrifty genotype, but there is no available information on the effects of metformin therapy. The relative effects of lifestyle and metformin on patterns of growth, fattening, metabolic status and attainment of puberty were assessed in females of an obese swine model (Iberian gilts), allocated to three experimental groups (group A, obesogenic diet and scarce exercise; group DE, adequate diet and opportunity for exercise; and group DEM, adequate diet and opportunity for exercise plus metformin). Group A evidenced high weight, corpulence and adiposity, high plasma triglycerides and impairments of glucose regulation predisposing to insulin resistance. These features were favourably modulated by adequate lifestyle (group DE), and these effects were strengthened by metformin treatment (group DEM), which induced an improvement in body development by favouring muscle deposition. However, contrary to expectations, metformin advanced the onset of puberty. Metformin treatments would have positive effects on growth patterns, adiposity and metabolic features of young females from ethnicities with thrifty genotype or developing leptin resistance, but a negative effect by advancing the attainment of puberty. This study provides a warning regarding the use of metformin, without further studies, in girls from these ethnicities.

MeSH terms

  • Adiposity / drug effects
  • Age Factors
  • Animals
  • Biomarkers / blood
  • Blood Glucose / metabolism
  • Diet, High-Fat
  • Disease Models, Animal
  • Energy Metabolism / drug effects*
  • Energy Metabolism / genetics
  • Female
  • Genotype
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / toxicity
  • Insulin / blood
  • Insulin Resistance
  • Magnetic Resonance Imaging
  • Metformin / pharmacology*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / growth & development
  • Obesity / blood
  • Obesity / drug therapy*
  • Obesity / genetics
  • Obesity / metabolism
  • Obesity / physiopathology
  • Phenotype
  • Risk Assessment
  • Sedentary Behavior
  • Sexual Maturation / drug effects*
  • Swine
  • Triglycerides / blood
  • Weight Gain / drug effects

Substances

  • Biomarkers
  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Triglycerides
  • Metformin