Curcumin Attenuates Lipopolysaccharide-Induced Hepatic Lipid Metabolism Disorder by Modification of m6A RNA Methylation in Piglets

Abstract

N6-methyladenosine (m6A) regulates gene expression and affects cellular metabolism. In this study, we checked whether the regulation of lipid metabolism by curcumin is associated with m6A RNA methylation. We investigated the effects of dietary curcumin supplementation on lipopolysaccharide (LPS)-induced liver injury and lipid metabolism disorder, and on m6A RNA methylation in weaned piglets. A total of 24 Duroc × Large White × Landrace piglets were randomly assigned to control, LPS, and CurL (LPS challenge and 200 mg/kg dietary curcumin) groups (n = 8/group). The results showed that curcumin reduced the increase in relative liver weight as well as the concentrations of aspartate aminotransferase and lactate dehydrogenase induced by LPS injection in the plasma and liver of weaning piglets (p < 0.05). The amounts of total cholesterol and triacylglycerols were decreased by curcumin compared to that by the LPS injection (p < 0.05). Additionally, curcumin reduced the expression of Bcl-2 and Bax mRNA, whereas it increased the p53 mRNA level in the liver (p < 0.05). Curcumin inhibited the enhancement of SREBP-1c and SCD-1 mRNA levels induced by LPS in the liver. Notably, dietary curcumin affected the expression of METTL3, METTL14, ALKBH5, FTO, and YTHDF2 mRNA, and increased the abundance of m6A in the liver of piglets. In conclusion, the protective effect of curcumin in LPS-induced liver injury and hepatic lipid metabolism disruption might be due to the increase in m6A RNA methylation. Our study provides mechanistic insights into the effect of curcumin in protecting against hepatic injury during inflammation and metabolic diseases.