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

白藜芦醇通过肾素-血管紧张素系统改善母体和断奶后高脂饮食引起的非酒精性脂肪肝

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作者:Mao-Meng Tiao, Yu-Ju Lin, Hong-Ren Yu, Jiunn-Ming Sheen, I-Chun Lin, Yun-Ju Lai, You-Lin Tain, Li-Tung Huang, Ching-Chou Tsai

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.

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.

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.

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