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

• Published in: Experimental physiology Vol. 99; no. 9; pp. 1241 - 1252
• Main Authors: Astiz, S., Gonzalez‐Bulnes, A., Astiz, I., Barbero, A., Perez‐Solana, M.L., Garcia‐Real, I.
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-09-2014
• Subjects: 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 Lifestyle; Sexual Maturation - drug effects; Swine; Triglycerides - blood; Weight Gain - drug effects
• ISSN: 0958-0670; 1469-445X
• DOI: 10.1113/expphysiol.2014.081455

New Findings
What is the central question of this study?
What is the effect of prepuberal metformin therapy and lifestyle in an obese swine model (Iberian gilts) with thrifty genotype on patterns of growth, fattening, metabolic status and attainment of puberty?
What is the main finding and its importance?
An obesogenic diet had deleterious effects on corpulence, adiposity and metabolic parameters. These features were favourably modulated by adequate lifestyle and metformin treatment, which favoured muscle deposition. However, metformin advanced the onset of puberty, which would be a negative effect. This provides a warning about the use of metformin, without further studies, in girls from ethnicities with thrifty genotype.
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.