Early responses of intestinal lamina propria ILCs to high fat diet regulate the development of obesity 3115

Abstract Description Alteration of innate immune cells homeostasis is believed to drive obesity and associated metabolic disorders. In this regard, little is known about gut ILC responses to obesity-driving diet. It is also unclear whether, or not ILCs could drive adipose tissue growth and weight gain. Using mice lacking Paneth cells as a model of extreme gastrointestinal distress, we show that weight gain follows a wave of changes in ILCs in the gut and adipose tissues. Specifically, we report that dysbiosis in Paneth cell deficient mice is associated with an alteration of the profile of ILCs in the gut and a significant increase in ILC2s while ILC3s were reduced. Analysis of gut and adipose tissues showed that initial exposure (2 weeks) to high fat diet (HFD) significantly increases ILC1s in the intestinal lamina propria and abdominal fat of Paneth cell KO mice, but not control mice. Interestingly, these changes occurred before change of overall body weight. Additional exposure (2 more weeks) to HFD further increased the number of ILC1s in abdominal fat tissues in the Paneth cell KO mice, while also increasing the number of inflammatory macrophages and B cells in these sites. The weight gain after further exposure to HFD was significantly greater in Paneth cell KO mice suggesting that the altered innate immune cell environments drove the development of obesity and metabolic disorders. Molecular mechanisms underlying stimulation of obesity by gut ILC subsets are being investigated. Funding Sources T32HL149637; NIH RO1 Topic Categories Mucosal and Regional Immunology (MUC)