Obesity is now a plague in developed countries and more than one third of U.S. adults are obese. Gut microbiota plays profound roles in host energy harvest, metabolism and inflammatory response associated with the development of obesity. Dusp6-deficient mice have been shown to be resistant to diet-induced-obesity (DIO) but the mechanism is still unclear. Using a gnotobiotic mouse model, we found that the transplantation of fecal/gut microbiota derived from dusp6-deficient mice can significantly increase energy expenditure and reduce weight-gain of the recipient mice. By analyzing fecal 16s rRNA genes, dusp6-deficient mice have different composition of gut microbiota when compared with wild-type mice. We also demonstrated that dusp6-deficient mice were resistant to DIO-mediated dysbiosis of gut microbiota. Upon further analysis of the intestinal transcriptome, we found that dusp6 deficiency is an important regulator of several metabolic pathways and genes related to intestinal barrier. Moreover, our analyses have shown that dusp6-deficient mice could alleviate DIO-induced inflammation.. This study demonstrates that dusp6 deficiency is a strong genetic factor that dominates diet effect on shaping gut microbiota and it remodels mucosal immunity to retain HFD-resistant homeostasis of gut microbiota. Our findings shed lights on obesity and obesity-derived metabolic disease treatment with novel therapeutic candidates/strategies such as DUSP6 pharmacological inhibitors and the development of microbiota-based therapeutics.
Date:
2016-05
Relation:
Journal of Immunology. 2016 May;196(1 Suppl.):Meeting Abstract 67.15.
