Dietary-induced effects on the intestinal expression of Wnt signaling molecules in C57BL/6J mice

Obesity and metabolic comorbidities such as nonalcoholic fatty liver disease (NAFLD) are increasingly associated with defects in the intestinal barrier. In previous work we have shown that a high-fat and high-sugar diet, so called Western-Style diet (WSD) resulted in a dysfunction of the intestinal barrier in C57BL/6J mice which led to a deterioration of the intestinal integrity and an increased bacterial translocation. Furthermore, we found a reduced Paneth cell cryptdin mRNA expression in the ileum of these mice. Conversely, supplementation with the prebiotic inulin or the short-chain fatty acid butyrate resulted in an increase in Paneth cell cryptdins. The Wnt signaling pathway, which is known to control stem cell function and epithelial proliferation, affects the final maturation and biological function of Paneth cells by regulating the expression of Paneth cell antimicrobials.

We therefore investigated the effect of a 12-week WSD ± fructose diet and a WSD ± fructose diet enriched with the prebiotic inulin (10 %) or the short-chain fatty acid (SCFA) sodium butyrate (5 %) on the expression of Wnt signaling effectors in the small intestine of C57BL/6J mice. The expression of the Wnt ligands Wnt3, Wnt5a, Wnt9a and the LRP6 co-receptor was determined by quantitative real-time PCR.

WSD diet or WSD with additional fructose had no significant effect on the mRNA expression of the Wnt-ligands Wnt3, Wnt5a and Wnt9a in the ileum compared to a control diet (CD). These results suggest that the diet-induced reduction in antimicrobial peptides was mainly subject to other regulatory mechanisms. Interestingly, supplementation with inulin and sodium butyrate led to a significant reduction of Wnt3 mRNA expression (p < 0.05) and Wnt5a mRNA expression (p <  0.01). In contrast, mRNA expression of the Wnt ligand Wnt9a and the LRP6 co-receptor (p <  0.05) was significantly increased by supplementation with inulin and sodium butyrate.

Our results demonstrate that the prebiotic inulin and the short-chain fatty acid (SCFA) sodium butyrate selectively modulate the expression of Wnt ligands and LRP coreceptor. The knowledge of the molecular mechanisms regulating the response to dietary interventions may help to develop more effective preventive and therapeutic strategies for diet-induced obesity.

Publication History

Article published online:
16 June 2020