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

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 d 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.