Early Metformin Treatment Improves Pancreatic Function and Prevents Metabolic Dysfunction in Early Overfeeding Male Rats at adulthood.

NEW FINDINGS What is the central question of this study? Studies reported the efficacy of metformin as a promising drug for prevent or treating metabolic diseases. Nutrient stresses during neonatal life increase long-term offspring risk for cardiometabolic diseases. Can early metformin treatment prevent the early overfeeding malprogramming effects? What is the main finding and its importance? Neonatal metformin treatment prevents early overfeeding-induced metabolic dysfunctions in adult rats. The inhibition of early hyperinsulinemia and adult hyperphagia may be associated with decreased metabolic disease risk in these animals. Therefore, interventions during infant development, offer a key area for future research to identify potential strategies to prevent the long-term metabolic diseases. We suggested that Metformin is a potential tool for intervention. ABSTRACT Because of the need for studies investigating the possible long-term effect of metformin use at critical stages of development, and taking into account the concept of metabolic programming, the present work aimed to evaluate whether early metformin treatment may program rats to resist the development of adult metabolic dysfunctions caused by overnutrition during lactation. Wistar rats raised in small litters (SLs, 3 pups/dam) and normal litters (NLs, 9 pups/dam) were used as models of early overfeeding and normal feeding, respectively. During the first 12 days of lactation, animals from SL and NL groups received metformin (M), while the controls received saline (S) injections. Biometric and biochemical parameters were assessed when rats were 90 days old. Food intake and bodyweight were monitored from weaning until rats reached 90 days of age. The metformin treatment decreased insulin levels in pups from SL groups, and as adults, these animals showed improvements in glucose tolerance, insulin sensitivity, body weight gain, white fat pad stores, and food intake. Low glucose insulinotropic effects were observed in pancreatic islets from both NL and SL groups. These results indicate that early postnatal treatment with metformin inhibits early overfeeding-induced metabolic dysfunctions in adult rats. This article is protected by copyright. All rights reserved.