Resveratrol ameliorates maternal and postweaning high-fat diet-induced nonalcoholic fatty liver disease via renin-angiotensin system

Background: Nonalcoholic fatty liver disease (NAFLD) can develop in prenatal stages and can be exacerbated by exposure to a postnatal high fat (HF) diet. We investigated the protective effects of resveratrol on prenatal and postnatal HF diet induced NAFLD. Methods: Male Sprague-Dawley rat offspring were placed in five experimental groups (n = 10-12 per group) normal diet (VNF), maternal HF diet (ONF), postnatal HF diet (VHF), and maternal HF diet/postnatal HF diet (OHF). A therapeutic group with resveratrol for maternal HF diet/postnatal HF diet (OHFR) was used for comparison. Resveratrol (50 mg/kg/ day) was dissolved in drinking water for offspring from post weaning to postnatal day (PND) 120. Results: We found that HF/HF-induced NAFLD was prevented in adult offspring by the administration of resveratrol. Resveratrol administration mediated a protective effect on rats on HF/HF by regulating lipid metabolism, reducing oxidative stress and apoptosis, restoring nutrient-sensing pathways by increasing Sirt1 and leptin expression, and mediating the renin angiotensin system (RAS) to decrease angiotensinogen, renin, ACE1, and AT1R levels and increased ACE2, AT2R and MAS1 levels compared to those in the OHF group. Conclusion: Our results suggest that a maternal and post weaning HF diet increases liver steatosis and apoptosis via the RAS Resveratrol might serve as a therapeutic target by mediating protective actions against NAFLD in offspring exposed to a combination of maternal and postnatal HF diet.