Improvement of the hepatic lipid status in intrauterine growth retarded pigs by resveratrol is related to the inhibition of mitochondrial dysfunction, oxidative stress and inflammation

Abstract

Mitochondrial dysfunction, oxidative stress and inflammation are crucial contributors to liver damage and nonalcoholic fatty liver disease (NAFLD) in adulthood in offspring affected by intrauterine growth retardation (IUGR). Resveratrol (RSV) has been reported to treat and/or prevent hepatic diseases under various pathological conditions. However, the therapeutic and/or preventive effects of RSV on hepatic abnormality in IUGR adults have not been investigated until now. The effects of IUGR and RSV on the hepatic metabolic status, mitochondrial function, redox homeostasis and inflammation in pigs in adulthood were investigated. A total of 36 pairs of IUGR and normal birth weight piglets were orally fed with 80 mg RSV per kg body weight per d or vehicle (0.5% carboxymethylcellulose) for 7–21 d after birth. And then the offspring were fed with a basal diet supplemented with 300 mg RSV per kg feed or a basal diet from weaning to slaughter at 150 d. The plasma and liver samples were collected for subsequent analysis. RSV exerted beneficial effects on hepatic injury and metabolic alterations in IUGR pigs, which may be due to improved mitochondrial function and fatty acid oxidation by intensified mitochondrial biogenesis, enhanced antioxidant levels such as glutathione reductase and total superoxide dismutase activities, increased interleukin 10 gene expression and repolarization of macrophages. RSV alleviated hepatic lipid accumulation in IUGR pigs by improving mitochondrial function, redox status and inflammation, implying that it is a potential candidate for further development as an effective clinical treatment for NAFLD associated with IUGR.