Mechanisms of metabolic changes in the conditions of insulin resistance and obesity induced by high fat diet in ileum of C57BL/6 mice

Context: The consumption of high fat diet causes great changes in many aspects of organism’s normal function, affecting metabolic processes, altering genes’ expression and enzymes’ action. The processes that take place after feeding high fat diet are established in many organs. However, in ileum they have not been fully explored. Objective: The final goal was to highlight new mechanisms, linking genes, transcriptional factors, environmental factors and microbiome in intestinal tract (with particular attention to the ileum) during high fat diet feeding. Design and methods: Ileal tissue samples of two experimental groups were used in the experiment (normal diet group and high fat diet group). Genes and proteins were evaluated by Real-time PCR and Western Blot respectively. For establishing of the associations Spearman correlation, linear regression and bootstrapping procedure were used. Results: The expression of HDAC3, SIRT1, FOXO1, PGC1-alpha, PPAR-alpha, CD36, PDK4, CPT1A and ACAA2 was enhanced in high fat diet group (p<0,05). AcFOXO1 protein was more abundant in ileum of ND group compared to HFD group. Strong association was discovered for HDAC3/PGC1-alpha, HDAC3/PPARA, HDAC3/FOXO1, PGC-1-alpha/PPARA, PGC-1-alpha/FOXO1, PGC-1-alpha/CD36, PPARA/FOXO1, PDK4/CPT1A, PDK4/ACAA2, CPT1A/ACAA2, SIRT1/CPT1A, SIRT1/ACAA2 and for AC-FOXO1/SIRT1, AC-FOXO1/CPT1A, AC-FOXO1/ACAA2 (according to western blot results). Conclusion: The results suggest that the role of the small intestine in the adaptation to high fat diet is not limited only to a simple nutrient-receiving station. The processes of the adaptation to high fat diet in ileum is organ-specific and their main characters are SIRT1, HDAC3, FOXO1, PGC1-alpha, PPAR-alpha and PDK4.