4-Octyl Itaconate Supplementation Relieves Soybean Diet-Induced Liver Inflammation and Glycolipid Metabolic Disorders by Activating the Nrf2-Pparγ Pathway in Juvenile Gibel Carp.

Abstract

Itaconate is a promising new candidate for anti-inflammatory and metabolic reprogramming, and 4-octyl itaconate (OI) is a cell-permeable itaconate derivative. To investigate the effect of OI in inflammatory response and glycolipid metabolism, we fed gibel carp with a 40% dietary soybean meal diet containing 0.1% OI (SBM + 0.1OI) or not (SBM) and compared these with fishmeal (FM) as reference. Compared with FM, dietary SBM decreased the growth performance, induced inflammation in the intestine and liver, and decreased the glucose utilization ability of the liver. However, 0.1% OI supplementation in SBM significantly increased the growth performance (from 20.11 ± 0.77 to 23.33 ± 0.45 g, P < 0.05), reduced inflammation in different organs through Nrf2 activation, and alleviated SBM-induced high plasma glucose (from 6.06 ± 0.23 to 4.37 ± 0.14 g, P < 0.05) and low crude body lipid (from 4.08 ± 0.17 to 4.91 ± 0.10 g, P < 0.05). Multi-omics revealed that OI had obvious effects on carbohydrate metabolism. OI regulates peroxisome proliferator-activated receptor gamma (ppar-γ), and its target genes (glut2 and gk) enhance liver glycolysis and lipid de novo lipogenesis, which are also dependent on Nrf2 activation. To conclude, dietary 0.1% OI can promote the growth of gibel carp and alleviate foodborne intestinal and hepatic inflammation and abnormal glycolipid metabolism by Nrf2-regulated Pparγ expression.