biostudies-literatureLi BFoundation of Gansu Key Laboratory of Protection and Utilization for Biological Resources and Ecological Restoration in LongdongIndustrial Support Project of Colleges and Universities in Gansu ProvinceNational Natural Science Foundation of ChinaStudent Innovation and Entrepreneurship Action Plan of Lanzhou UniversityNatural Science Foundation of Gansu ProvinceScience and Technology Program of Qingyang City771-792https://www.ebi.ac.uk/biostudies/studies/S-EPMC11073502biostudies-literatureUnknown14(5)High-fat diet (HFD)-fed mice have been widely used in the clinical investigation of obesity. However, the long-term effect of HFD on gut microbiota and metabolites, plasma and liver metabolomics, colonic and liver transcriptomics remain largely unknown. In this study, 6-week-old C57BL/6J male mice fed with HFD for 14 weeks showed increased obesity-related indexes including alanine aminotransferase, aspartate aminotransferase, total cholesterol, total triglyceride, free fatty acids, lipopolysaccharides, IL-6, and TNFα. Furthermore, microbial diversity and richness were also significantly decreased. In the colon, genes involved in tryptophan metabolism, PPAR signaling pathway, cholesterol metabolism, and lipid localization and transport, were upregulated. While in the liver, MAPK signaling aFEBS open bioIn-depth multiomic characterization of the effects of obesity in high-fat diet-fed mice.PMC1107350221JR7RA39881960165QY-STK-2023A-0302020C-242023005003822JR5RM210LDSWZY202103QY2021A-F021Liu XYang YWang QChen JXiang XLi BOu XXu ZfalseIn-depth multiomic characterization of the effects of obesity in high-fat diet-fed mice.High-fat diet (HFD)-fed mice have been widely used in the clinical investigation of obesity. However, the long-term effect of HFD on gut microbiota and metabolites, plasma and liver metabolomics, colonic and liver transcriptomics remain largely unknown. In this study, 6-week-old C57BL/6J male mice fed with HFD for 14 weeks showed increased obesity-related indexes including alanine aminotransferase, aspartate aminotransferase, total cholesterol, total triglyceride, free fatty acids, lipopolysaccharides, IL-6, and TNFα. Furthermore, microbial diversity and richness were also significantly decreased. In the colon, genes involved in tryptophan metabolism, PPAR signaling pathway, cholesterol metabolism, and lipid localization and transport, were upregulated. While in the liver, MAPK signaling a2024-01-01T00:00:00Z2024 May2026-06-01T17:26:48.393Z2026-04-08T14:14:14.377ZS-EPMC110735023847998310.1002/2211-5463.13788