METFORMIN DURING ADULTHOOD CANNOT ATTENUATE THE HARMFUL EFFECTS OF NEONATAL OVERNUTRITION

Abstract

Under- or overnutrition, during critical periods of development, lead to the development of
obesity and cardiometabolic dysfunction later in life in rats that have been programmed for
the development of metabolic dysfunction in a litter reduction model. On day 1, all litters are
standardized to 9 pups per dam and on day 3 after birth, litters were adjusted to 3 pups per
dam in the small litter group (SL) and the NL group remained with 9 animals. At 70 days of
age, the animals were separated into 2 new groups: Saline (SAL) and Metformin (MET). For
12 days, the NL and SL animals were treated daily with saline, giving rise to the NL-SAL and
SL-SAL groups, or were treated with Met 100mg/kg/day, giving rise to the NL-MET and SL-
MET groups. The treatment ended at 82 days of age and the animals were taken up to 142
days of life. Body weight remained significantly higher in SL compared to NL animals up to
142 days (p<0.0001), with no significant difference in relation to treatment. And the same
was observed in relation to glucose intolerance and insulin resistance (p<0.0001). We can
conclude that short-term treatment with metformin did not attenuate the metabolic
dysfunction induced by neonatal overnutrition.