Abstract 038: Adipocyte-specific BBSome Deficiency Impacts The Sympathetic Nervous System And Baroreceptor Reflex Sensitivity

Abstract

The BBSome, a protein complex of 8 Bardet-Biedl syndrome (BBS) proteins including BBS1, has emerged as an important regulator of metabolic, cardiovascular, and autonomic functions. Patients with Bbs gene mutations display severe obesity, type II diabetes and hypertension. Previous studies demonstrated that neuronal BBSome contributes to metabolic homeostasis and blood pressure regulation, however the importance of adipocyte BBSome in controlling glucose homeostasis and blood pressure remains poorly understood. To address this, we generated mice lacking the BBSome specifically in adipocytes through selective deletion of the Bbs1 gene (Adipo Cre /Bbs1 fl/fl ) by crossing the adiponectin Cre (Adipo Cre ) male mice crossing with female Bbs1 floxed (Bbs1 fl/fl ) mice. Adipocyte-specific Cre recombinase was validated by further crossing the Adipo Cre mice with td-Tomato reporter mice. Bbs1 gene deletion in adipocytes was confirmed by measuring Bbs1 gene expression in adipose tissue using qRT-PCR. To induce obesity, mice were fed a high fat high sucrose diet (HFHSD) for 16 weeks starting at 4 weeks of age. Interestingly, the weight gain evoked by HFHSD was comparable between male and female Adipo Cre /Bbs1 fl/fl mice and littermate controls. Similarly, Adipo Cre /Bbs1 fl/fl mice displayed unaltered blood glucose as indicated by glucose and insulin tolerance tests. Using radiotelemetry, we found no significant difference in systolic, diastolic, and mean arterial pressure and heart rate between control and Adipo Cre /Bbs1 fl/fl mice fed HFHSD. Surprisingly, a significant increase in renal sympathetic nerve activity was observed in Adipo Cre /Bbs1 fl/fl mice (Control: 101.1 ± 16.23 spikes/sec, Adipo Cre /Bbs1 fl/fl : 133.2 ± 32.15 spikes/sec, p < 0.05). Next, we measured baroreceptor reflex sensitivity by analyzing the responses to sodium nitroprusside (SNP) and phenylephrine (PE). The slope analysis showed that Adipo Cre /Bbs1 fl/fl mice were less sensitive to SNP (Control: -2.56 ± 0.82, Adipo Cre /Bbs1 fl/fl : -1.746± 0.29, p < 0.05), demonstrating altered baroreflex. Taken together, our data implicate the adipocyte BBSome is a regulator of sympathetic nervous activation and baroreflex sensitivity.