Abstract 125: Elevated Bacterial Fatty Acid Metabolism And Fecal Calorific Values Are Associated With Reduced Diet-induced Adiposity And Weight Gain In Mice

Abstract

Introduction: Activation of the sympathetic nervous system (SNS) leads to exaggerated immune responses in cardiometabolic conditions. We previously showed that ablation of beta-adrenergic receptors (ADRB) on the bone marrow (BM) hematopoietic cells reduces blood pressure, dampens the immune responses, and modifies gut microbiota, suggesting multisystem host-microbiota interactions. To investigate the role of the microbiota in these complex interactions, we tested the effects of high fat diet (HFD) on the gut microbiota and adiposity in BM mouse chimera characterized by reduced SNS-immune signaling. Methods: Male C5BL/6 wild type (WT) mice were irradiated and reconstituted with BM cells from either the C57BL/6 WT controls or the ADRB 1/2 knock-out mice (KD) to generate BM chimera. Following recovery, mice were fed with a control diet (CNT) or HFD for two weeks ad libitum . Food intake and body weights were measured weekly, and body fat (NMR) and visceral fat pad weights were measured at endpoint. At endpoint, 16S sequencing and metagenomic analyses (QIIME2, PiCRUST2) were performed in cecal samples, and residual fecal calorific values were determined using a simultaneous thermogravimetric analyzer differential calorimeter (TA Instruments). Results: No change in food intake was observed in either group. However, significant increases in body weight, total body fat, and visceral fat weight were observed in the WT compared to KD chimera on HFD ( p<0.05) . HFD elevated gut bacterial Shannon α-diversity (p< 0.05) in the WT but not the KD chimera, and we observed a decrease in g_Faecalibacterium and p_Actinobacteria in WT, and an increase in p_Bacteroidetes and o_Bacteroidales in the KD mice on HDF. Enrichment in fatty acid metabolic pathways and increased fecal calorific values were observed in the KD compared to WT chimera on HFD ( p<0.05) . Conclusion: Reduced SNS-immune signaling is protective against diet-induced weight gain and body fat accumulation. This may in part be mediated by the gut microbiota, reflecting in increased bacterial fatty acid metabolism and elevated residual fecal calorific values, suggesting reduced fat absorption. We propose that selective enrichment of gut bacteria is a potential therapeutic target in diet-induces obesity.