This study was designed to first investigate the effects of zinc phytate (ZnPA) from wheat bran in alleviating high-fat diet (HFD)-induced hepatic inflammation and metabolic disorders and its underlying mechanism. C57BL/6J mice were randomly assigned to five groups including normal diet (ND), HFD, HFD+low-dose ZnPA (100 mg/kg), HFD+high-dose ZnPA (200 mg/kg), and HFD+wheat bran (100 mg/kg). All interventions were administered orally for 12 weeks. The results indicated that ZnPA significantly mitigated HFD-induced weight gain, dyslipidemia, pathoglycemia, hepatic steatosis and inflammation (p < 0.05). ZnPA effectively corrected HFD-induced microbial dysbiosis, in which the relative abundance of the Ruminococcus torques group decreased from 11.0% to 0.75%, and Coriobacteriaceae_UCG-002 dropped from 2.47% to 0.087% (p < 0.05). Conversely, ZnPA increased the abundance of Ileibacterium from 0.32% to 17.76% and Dubosiella from 1.03% to 4.24% (p < 0.05). Meanwhile, ZnPA could be metabolized by the gut microbiota to release IP6, which was further converted into secondary inositol phosphates (InsP3–5), resulting in increases of 52.1%, 83.3%, 62.5%, and 96.2% in the colonic contents of InsP6, InsP5, InsP4, and InsP3 (p < 0.05), respectively. In addition, ZnPA increased levels of secondary bile acids and short-chain fatty acids, especially deoxycholic acid and taurocholic acid, which were elevated by 1.95-fold and 1.88-fold (p < 0.05), respectively. Interestingly, ZnPA enhanced hepatic expressions of histone deacetylase 3, bile acid receptor FXR, and lipid metabolism coactivator PGC-1α (p < 0.05). Collectively, these results indicated that ZnPA might alleviate obesity-related hepatic inflammation and metabolic disorders by reshaping microbial composition and increasing the production of microbial metabolism such as secondary bile acids, thereby triggering FXR–PGC1α axis activation.
