A Inibição do pico da secreção de leptina aos 30 dias reverte as alterações metabólicas em ratos programados pela leptina na lactação

Abstract

Hyperleptinemia during lactation programs for higher serum leptin in 30 and 180 days old rats, higher body mass and related metabolic changes. Our aim was to evaluate the inhibition of serum leptin at 29 and 30 days old on the metabolic phenotype of rats programmed with leptin during lactation. Pups from Wistar rats were saline-injected (C) or leptin-injected (L 8µg/100g BW) from 1 to 10 postnatal days. At 29 and 30 days old the animals from both groups were injected with anti-leptin antibody (3µg/100gPC LA and CA) or saline (LS and CS). The higher visceral (VFM) (+53%) and total fat mass (TFM) (+33%), hyperleptinemia (+67%) hypertriglyceridemia (+47%) and lower adiponectinemia (-44%) observed in LS group compared to CS were prevented by immunoneutralization of leptin, since LA group had those parameters values similar to CS group. However, the immunoblockade of leptin in normal animals led to the same metabolic changes seen in leptin- treated animals, in addition to a lower serum adiponectin (-74% versus CS) and higher insulin resistance index (+37%). Hepatic SIRT1, a histone/protein deacetilase, was higher (+41%) only in LA group, suggesting a role for SIRT1 and possible epigenetic mechanisms in prevention of leptin programming. Therefore, our data suggest that one week after weaning is also a critical period for metabolic imprinting and that either lack or excess of leptin programs for unfavorable metabolic phenotype at adulthood. Remarkably, inhibitions of hyperleptinemia effects in 30 day-old rats abolish most of the leptin-programmed unfavorable metabolic phenotype, which represents a promising strategy for prevention or treatment of these metabolic dysfunctions