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.