Short-term Treatment with Metformin During Puberty Mitigates Metabolic Dysfunctions Programmed by Neonatal...

Area of Science:

• Metabolic health
• Developmental biology
• Pharmacology

Background:

• Neonatal overfeeding leads to obesity and metabolic dysfunction.
• Early-life factors significantly influence long-term health outcomes (Developmental Origins of Health and Disease concept).
• Childhood obesity has severe, lasting health consequences.

Purpose of the Study:

• To investigate if short-term metformin treatment during puberty can prevent metabolic dysfunction caused by neonatal overfeeding.
• To determine if metformin intervention in adulthood has similar effects on metabolic programming.

Main Methods:

• Male Wistar rats were raised in small (overfed) or normal litters.
• Metformin or saline was administered during puberty (days 35-42) or adulthood (days 70-81).
• Metabolic parameters, body weight, and tissue fat accumulation were assessed post-intervention.

Main Results:

• Neonatally overfed rats (SL) showed significant metabolic dysfunction, increased weight, and fat accumulation compared to controls (NL).
• Pubertal metformin treatment in SL rats reduced white adipose tissue, liver weight, and weight gain.
• Metformin treatment initiated in adulthood did not alter metabolism or prevent long-term metabolic changes.

Conclusions:

• Short-term metformin treatment during puberty mitigates adult metabolic dysfunction from neonatal overnutrition in rats.
• Metformin intervention in adulthood did not produce lasting metabolic improvements.
• Findings support the critical window for intervention highlighted by the DOHaD concept.