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

Abstract

N -methyladenosine (m A) regulates gene expression and affects cellular metabolism. In this study, we checked whether the regulation of lipid metabolism by curcumin is associated with m A RNA methylation. We investigated the effects of dietary curcumin supplementation on lipopolysaccharide (LPS)-induced liver injury and lipid metabolism disorder, and on m A 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 m A 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 m A RNA methylation. Our study provides mechanistic insights into the effect of curcumin in protecting against hepatic injury during inflammation and metabolic diseases.

Resveratrol Attenuates Aflatoxin B1-Induced ROS Formation and Increase of m6A RNA Methylation

“…These results highlight the effective protection of resveratrol in AFB 1 -induced liver injury. Fascinatingly, emerging observations indicated that nutritional challenges, such as a high-fat diet, a dietary fasting state, and dietary supplement with betaine, cycloleucine, and curcumin [20,46] regulate the gene expression by m 6 A RNA methylation. Here, we also found that dietary resveratrol supplementation in AFB 1 -treated mice significantly reduced the level of m 6 A compared with the AFB 1 group.…”

RNA N6-methyladenosine: a promising molecular target in metabolic diseases

“…Increased FTO levels are also highly involved in hepatic oxidative stress and lipid deposition which participate in the process of NAFLD [99]. Currently, dietary curcumin can affect the expression of METTL3, METTL14, ALKBH5, FTO, and YTHDF2 mRNAs, and finally improve lipopolysaccharide-induced liver injury and hepatic lipid metabolism disruption by increasing m 6 A methylation level in the liver of piglets [104]. In addition, the knockdown of METTL3 or YTHDF2 can increase the lifetime and expression of peroxisome proliferator activated receptor alpha (PPARα) mRNA, resulting in a reduction of lipid accumulation [105].…”

METTL3 Attenuates LPS-Induced Inflammatory Response in Macrophages via NF-κB Signaling Pathway

“…During the past few years, the role of N 6 -methyladenosine (m 6 A) methylation of RNA in autoimmunity, inflammation, and cancer has drawn close attention [7][8][9][10]. m 6 A is the most common posttranscription modification of RNA [11].…”