Introduction: Adipokines regulate whole-body energy homeostasis, insulin sensitivity and immunity by mediating the crosstalk between adipose tissues and multiple tissues, including liver, skeletal muscle, brain, pancreas and intestines. Recent studies revealed that intestines also exhibit insulin resistance and dysregulated immune homeostasis in obese condition. On the other hand, several adipokines including adiponectin and adipocyte fatty acid binding protein have been shown to regulate intestinal function. Here, we aim to investigate the relationship between the adipose tissue and gut homeostasis using lipodystrophy animal models.
Methods: We employed our recently developed lipodystrophic mouse model, in which adipocyte MDM2 is genetically deleted (so-called Adipo-MDM2-KO mice). In fat transplantation experiment, subcutaneous fat form their wild type (WT) littermates was transplanted to the Adipo-MDM2-KO mice for 8 weeks. To assess gut permeability, Adipo-MDM2-KO mice and their wild type (WT) littermates were orally gavaged with DX-4000-FITC for 1 hour. Circulating LPS level were measured using the endotoxin assays, which reflects gut permeability and endotoxemia. For assessment of gut morphology, ileum isolated from Adipo-MDM2-KO mice and their WT littermates were subjected to Haemotoxylin and Eosin (H and E) staining.
Results and Conclusion: Adipo-MDM2-KO mice exhibited impaired gut barrier function and altered gut microbiota composition when compared with the WT littermates. A higher level of DX-4000-FITC in the serum of Adipo-MDM2-KO mice were detected. In addition, circulating level of LPS was significantly increased in Adipo-MDM2-KO mice. H and E staining showed a change in gut morphology and an increased number of inflammatory cells in the ileum of Adipo-MDM2-KO mice. These results demonstrated that fat loss leads to intestinal dysfunction, therefore, the adipose tissue is required for gut homeostasis.
K. Long: None.
National Natural Science Foundation of China (91857119)