Gut Microbe <i>Rikenellaceae_RC9_gut_group</i> and <i>Knoellia</i> ‐Mediated Acetic Acid Regulates Glucose and Lipid Metabolism in the Muscle of Freshwater Drum ( <i>Aplodinotus grunniens</i> ) Under High‐Fat Diets

Metabolic disorders and complications induced by high-fat diets (HFDs) are a hot research topic in aquatic animal nutrition and health, but the mechanism of gut microbes and their metabolites on muscle homeostasis is not yet clear. In this study, a 16-week HFD (Con, 6% fat and HFD, 12% fat) rearing experiment was conducted with a freshwater drum (20.88 ± 2.75 g, about 20,000 fish per pond) to investigate the underlying regulation of gut microbes on muscle nutrient and metabolism. Results revealed that HFD had no remarkable effect on proximate nutrients (moisture, ash, crude protein, and crude fat), total amino acids, and fatty acids contents in muscle. Moreover, decreased acetic acid content by HFD in the gut and muscle was confirmed to regulate lipid metabolism, as evidenced by the activation of fatty acid synthesis (acetyl-CoA carboxylase alpha [ACC1] and sterol regulatory element binding protein-1 [SREBP1]) and inhibition of fatty acid lipolysis (AMP-activated protein kinase [AMPK], adipose triglyceride lipase [ATGL], and carnitine palmitoyl transferase 2 [CPT2]). Interestingly, RNA-seq revealed glycolytic metabolism (glycolysis/gluconeogenesis and pyruvate metabolism) was active in the muscle under HFD, which was further confirmed to be the intermediate for acetic acid to regulate lipid metabolism. Strikingly, gut microbe <i>Rikenellaceae_RC9_gut_group</i> and <i>Knoellia</i> regulate muscle lipid and glucose metabolism through their derived metabolite acetic acid, which is the key target for gut microbe to regulate muscle. Taken together, these results reveal the regulatory mechanism of gut microbes and derived metabolites on muscle metabolism and development, providing a theoretical basis for the healthy regulation of HFD in aquatic animals.