BackgroundExcessive consumption of high-fat diets is associated with disordered metabolic responses, which may lead to chronic diseases. High-fat diets containing different types of fatty acids lead to distinct alterations in metabolic responses of gut-brain axis.MethodsIn our study, normal male C57BL/6J mice were fed to multiple high fatty acid diets (long-chain and medium-chain saturated fatty acid, LCSFA and MCSFA group; n-3 and n-6 polyunsaturated fatty acid, n-3 and n-6 PUFA group; monounsaturated fatty acid, MUFA group; trans fatty acid, TFA group) and a basic diet (control, CON group) for 19 weeks. To investigate the effects of high-fat diets on metabolic responses of gut-brain axis in obese mice, blood lipids were detected by fast gas chromatography, and related proteins in brain and intestine were detected using Western blotting, ELISA, and immunochemistry analysis.ResultsAll high-fat diets regardless of their fatty acid composition induced obesity, lipid disorders, intestinal barrier dysfunction, and changes in gut-brain axis related factors except basal diet in mice. For example, the protein expression of zonula occludens-1 (ZO-1) in ileum in the n-3 PUFA group was higher than that in the MCSFA group (P < 0.05). The expressions of insulin in hippocampus and leptin in ileum in the MCSFA group significantly increased, compared with other groups (all Ps < 0.05).ConclusionThe high MCSFA diet had the most effect on metabolic disorders in gut-brain axis, but the high n-3 PUFA diet had the least effect on changes in metabolism.