Early redox imbalance is associated with liver dysfunction at weaning in overfed rats. (1st November 2015)

• Record Type: Journal Article
• Authors: Conceição, E. P. S.; Moura, E. G.; Carvalho, J. C.; Oliveira, E.; Lisboa, P. C.
• Is Part Of: Journal of physiology. Volume 593:Number 21(2015:Nov.)
• Page Start: 4799
• Page End: 4811
• Publication Date: 2015-11-01
• Subjects: Physiology -- Periodicals; 612.005
• DOI: 10.1113/JP271189
• Languages: English
• ISSNs: 0022-3751

Abstract

Abstract : Key points: Childhood obesity is associated with precocious oxidative stress, which can contribute to future diseases. Early overfed rats have increased oxidative stress in liver and plasma at weaning. The model of litter size reduction causes adipocyte hypertrophy and lower PPARγ at weaning, suggesting a decrease in adipocyte proliferation. Abstract: Neonatal overfeeding induced by litter size reduction leads to further obesity and other metabolic disorders, such as liver oxidative stress and microsteatosis at adulthood. We hypothesized that overfeeding causes an early redox imbalance at weaning, which could programme the animals to future liver dysfunction. Thus, we studied lipogenesis, adipogenesis, catecholamine status and oxidative balance in weaned overfed pups. To induce early overfeeding, litters were adjusted to three pups at the 3rd day of lactation (SL group). The control group contained 10 pups per litter until weaning (NL group). Peripheral autonomic nerve function was determined in vivo at 21 days old. Thereafter, pups were killed for further analysis. Differences were considered significant when P < 0.05. The SL pups presented with a higher visceral adipocyte area, higher content of lipogenic enzymes (ACC, FAS) and with a lower content of adipogenic factors (CEBP, PPARγ) in visceral adipose tissue (VAT). Although autonomic nerve activity and adrenal catecholamine production were not significantly altered, catecholamine receptor (β3ADR) content was lower in VAT. The SL pups also presented with higher triglyceride, PPARγ, PPARα and PGC1α contents in liver. In plasma and liver, the SL pups showed an oxidative imbalance, with higher lipid peroxidation and protein oxidation. The SL group presented with a higher serum alanine aminotransferase (ALT). The early increase in lipogenesis in adipose tissue and liver in weaned overfed rats suggests that the higher oxidative stress and lower catecholamine content in VAT are associated with the early development of liver dysfunction and adipocyte hypertrophy. Abstract :