Short-term Treatment with Metformin During Puberty Mitigates Metabolic Dysfunctions Programmed by Neonatal Overfeeding in Male Rats.

Overview

abstract

OBJECTIVE: To address the major public health problems of increased body weight and obesity, causing conditions such as hypertension and diabetes. Early obesity in childhood and adolescence has more severe long-term health consequences. The Developmental Origins of Health and Disease (DOHaD) concept examines how early overfeeding and other factors affect health throughout life. This study hypothesized that a short-term metformin treatment during puberty could reduce metabolic dysfunction caused by neonatal overfeeding. We investigated whether the same intervention would have a similar effect on metabolic programming in adulthood. METHODS: Male Wistar rats raised in small (SL, three pups per mother) and normal (NL, 9 pups per mother) litters were used as models of early overfeeding. Some of the SL and NL animals received intraperitoneal injections of metformin (NL-M and SL-M), whereas the controls received saline (NL-C and SL-C) from days 35-42 (puberty) or 70-81 (adulthood). RESULTS: Two months after the intervention, at both puberty and adulthood, the SL animals exhibited metabolic dysfunction, and were significantly heavier with greater tissue fat accumulation than the NL animals (p <0.0001). SL-M animals treated during puberty exhibited significant reductions in white adipose tissue and liver weight, as well as lower weight gain (p <0.05). In contrast, metformin treatment in adulthood did not alter metabolism. CONCLUSION: These findings suggest that short-term metformin treatment in rats during puberty can mitigate adult metabolic dysfunction induced by neonatal overnutrition. However, this intervention in adulthood did not result in long-term metabolic changes, which confirms the DOHaD concept.