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 Nrf2regulated Pparγ expression.

Enhancement of liver mitochondrial complex I and energy metabolism induced by enteritis: The key role of gut microbiota derived endotoxins

“…Our results showed that intestinal inflammation increases plasma LPS, and leads to liver damage. The same result was found in the SBM-induced intestinal inflammation model (16).…”

“…Several intestinal inflammation models have been created in fish to clarify the mechanisms of inflammatory reactions and evaluate novel prevention methods, including soybean meal (16), pathogenic bacteria Aeromonas hydrophila (17), and chemical reagent TNBS (18). In the present study, the histological examination revealed that TNBS caused typical intestinal pathology, including villus atrophy, inflammatory cells infiltrating the lamina propria and disruption of the epithelial barrier as reported previously (16,19).…”

“…Total RNA was extracted and the quality was checked using 1.0% agarose electrophoresis. Subsequently, the mRNA quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed as previously described (16). The specific primers used for RT-PCR are referenced in previous studies (16) and the additional primers are listed in Table 1.…”

“…Subsequently, the mRNA quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed as previously described (16). The specific primers used for RT-PCR are referenced in previous studies (16) and the additional primers are listed in Table 1. The expression levels in the intestine were calculated as fold-change in expression relative to the housekeeping gene (b-actin and ef-1a).…”

Aconitate decarboxylase 1 regulates glucose homeostasis and obesity in mice

“…Future studies will be important to test whether itaconate can mitigate PA‐induced insulin resistance through regulation of inflammatory signaling. Itaconate derivatives have been shown to suppress liver inflammation in models of disease [35–38], and it is unknown whether this has any impact on glucose homeostasis. Our data in 3T3‐L1 cells also implicated a possible role for Acod1 in adipocytes as either a potential producer of itaconate or as an effector cell.…”