Adipocyte-Specific Disruption of the BBSome Causes Metabolic and Autonomic Dysfunction

Obesity is a major public health issue due to its association with type 2 diabetes, hypertension, and other cardiovascular risks. The BBSome, a complex of 8 conserved Bardet-Biedl Syndrome (BBS) proteins, has emerged as a key regulator of energy and glucose homeostasis as well as cardiovascular function. However, the importance of adipocyte BBSome in controlling these physiological processes is not clear. Here, we show that adipocyte-specific constitutive disruption of the BBSome through selective deletion of the Bbs1 gene (Adipo^Cre/Bbs1^fl/fl mice) does not affect body weight under normal chow or high fat & high sucrose diet (HFHSD). However, constitutive BBSome defiency caused impairment in glucose tolerance and insulin sensitivity. Similar phenotypes were observed after inducible adipocyte-specific constitutive disruption of the BBSome (Adipo^CreERT2/Bbs1^fl/fl mice). Interestingly, a significant increase in renal sympathetic nerve activity, measured using multifiber recording in the conscious state, was observed in Adipo^Cre/Bbs1^fl/fl mice on both chow and HFHSD. A significant increase in tail-cuff arterial pressure was also observed in chow-fed Adipo^Cre/Bbs1^fl/fl mice, but this was not reproduced when arterial pressure was measured by radiotelemetry. Moreover, Adipo^Cre/Bbs1^fl/fl mice had no significant alterations in vascular reactivity. On the other hand, Adipo^Cre/Bbs1^fl/fl mice displayed impaired baroreceptor reflex sensitivity when fed HFHSD, but not on normal chow. Taken together, these data highlight the relevance of the adipocyte BBSome for the regulation of glucose homeostasis, sympathetic traffic. The BBSome also contribute to baroreflex sensitivity under HFHSD, but not normal chow.