METFORMIN DURING ADOLESCENCE ATTENUATES METABOLIC MARKERS IN ADULT RATS OVERFED DURING LACTATION

Resumen

The growing prevalence of obesity around the world requires a better understanding of this
pathophysiology and strategies to mitigate its deleterious effects. Obesity, related to lifestyle,
is also associated with the DOHAD concept or ontogenetic plasticity. On the other hand, the
administration of certain drugs in critical periods of development can inhibit or reverse this
situation. This study aims to evaluate the effects of metformin treatment during adolescence
on the metabolism of overfed rats during lactation. For this purpose, the litters were
standardized in 9 pups until the 3rd day of life, and later adjusted in Normal Litters (NL, 9
pups), and Reduced Litters (SL, 3 pups). At 30 days of age, they were subdivided into 4 new
groups: NL-saline gavage (NL-S), NL-metformin gavage (NL-M), SL-saline gavage (SL-S)
and SL-metformin gavage (SL-M). Metformin treatment (300 mg/kg body weight) was given
daily during adolescence (PN30-PN60). At the end of lactation (PN21), SL animals presented
a greater body mass and abdominal size. In contrast, at 120 days old, SL-M rats exhibited
better peripheral insulin sensitivity, oral glucose tolerance, visceral adiposity, and lipid profile
compared to SL-S rats. Metformin did not alter the metabolism of NL animals. In conclusion,
treatment with metformin during adolescence, in rats induced obesity by the litter reduction
model, was effective in attenuating signs of obesity and/or metabolic syndrome, as well as
restoring the glycemic homeostasis of these animals to levels similar to equivalent controls.