Affiliation:
1. Gansu Key Laboratory of Protection and Utilization for Biological Resources and Ecological Restoration in Longdong Longdong University Qingyang China
2. College of Medicine Longdong University Qingyang China
3. Cuiying Biomedical Research Center Lanzhou University Second Hospital Lanzhou China
4. College of Life Sciences and Technology Longdong University Qingyang China
5. Element Nutrition of National Health Commission, National Institute of Nutrition and Health China CDC Beijing China
6. Department of Endocrinology and Metabolism Lanzhou University Second Hospital Lanzhou China
Abstract
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 and unsaturated fatty acid biosynthesis were upregulated. Metabolomic analyses revealed decreased levels of glycerophospholipids and fatty acyl, but increased amino acids, coenzymes and vitamins, and organic acids in the colon, suggesting high absorption of oxidized lipids, while acyl‐carnitine, lysophosphatidylcholine, lysophosphatidylethanolamine, and oxidized lipids were reduced in the liver, suggesting a more active lipid metabolism. Finally, correlation analyses revealed a positive correlation between gut microbiota and metabolites and the expression of genes associated with lipid localization, absorption, and transport in the colon, and nutrients and energy metabolism in the liver. Taken together, our results provide a comprehensive characterization of long‐term HFD‐induced obesity in mice.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Gansu Province