EARLY PPARα ACTIVATION PROTECT AGAINST HEPATIC MICROSTEATOSIS INDUCED BY POST-NATAL OVERFEEDING

Abstract

Post-natal overfeeding leads to development of obesity and metabolic dysfunction. PPARα
activation improves steatosis and metabolic dysfunction associated with obesity. Thus, we
have hypothesized that PPARα would prevent the metabolic disorders and obesity caused by
litter reduction. Wistar male offspring rats were divided into normal litter (NL - 9 pups) and
small litter (SL - 3 pups) and were daily treated with an PPARα agonist, fenofibrate, from
post-natal day (PN) 1 until weaning (PN21), with either, fenofibrate (F - 12.5mg/kg) or
vehicle (V). Forming the following groups: NL-V, NL-F, SL-V, SL-F. At PN120 animals
were euthanized and histological evaluation of samples from liver, visceral (VAT),
subcutaneous (SAT) and brown (BAT) adipose tissue were performed. Fenofibrate was able
to prevent the development of microsteatosis in the liver caused by postnatal overfeeding. In
regard to VAT, there was no difference in the mean adipocyte area, however in distribution
analyzes it was observed higher frequency of larger adipocytes in SL groups, and no
difference was observed in SAT. SL-V animals had increased lipid area in BAT, which was
reduced in SL-F. Increased PPARα activation induced by an agonist during lactation
improved some histopathological abnormalities induced by postnatal overfeeding. This was
proven by the decrease in microsteatosis in the liver and improvement in VAT and BAT
morphology, thus implying a better metabolic health.