Yuying Zhao, Deng-Fu Guo, Donald A Morgan, Young-Eun Cho, Kamal Rahmouni
{"title":"Adipocyte-specific disruption of the BBSome causes metabolic and autonomic dysfunction.","authors":"Yuying Zhao, Deng-Fu Guo, Donald A Morgan, Young-Eun Cho, Kamal Rahmouni","doi":"10.1152/ajpregu.00039.2024","DOIUrl":null,"url":null,"abstract":"<p><p>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 eight 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 <i>Bbs1</i> gene adiponectin (<i>Adipo</i><sup>Cre</sup>/<i>Bbs1</i><sup>fl/fl</sup> mice) does not affect body weight under normal chow or high-fat and high-sucrose diet (HFHSD). However, constitutive BBSome deficiency caused impairment in glucose tolerance and insulin sensitivity. Similar phenotypes were observed after inducible adipocyte-specific disruption of the BBSome (<i>Adipo</i><sup>CreERT2</sup>/<i>Bbs1</i><sup>fl/fl</sup> mice). Interestingly, a significant increase in renal sympathetic nerve activity, measured using multifiber recording in the conscious state, was observed in <i>Adipo</i><sup>Cre</sup><i>/Bbs1</i><sup>fl/fl</sup> mice on both chow and HFHSD. A significant increase in tail-cuff arterial pressure was also observed in chow-fed <i>Adipo</i><sup>Cre</sup>/<i>Bbs1</i><sup>fl/fl</sup> mice, but this was not reproduced when arterial pressure was measured by radiotelemetry. Moreover, <i>Adipo</i><sup>Cre</sup>/<i>Bbs1</i><sup>fl/fl</sup> mice had no significant alterations in vascular reactivity. On the other hand, <i>Adipo</i><sup>Cre</sup>/<i>Bbs1</i><sup>fl/fl</sup> 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 and sympathetic traffic. The BBSome also contributes to baroreflex sensitivity under HFHSD, but not normal chow.<b>NEW & NOTEWORTHY</b> The current study show how genetic manipulation of fat cells impacts various functions of the body including sensitivity to the hormone insulin.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":null,"pages":null},"PeriodicalIF":2.2000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380988/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"American journal of physiology. Regulatory, integrative and comparative physiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1152/ajpregu.00039.2024","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/13 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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 eight 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 adiponectin (AdipoCre/Bbs1fl/fl mice) does not affect body weight under normal chow or high-fat and high-sucrose diet (HFHSD). However, constitutive BBSome deficiency caused impairment in glucose tolerance and insulin sensitivity. Similar phenotypes were observed after inducible adipocyte-specific disruption of the BBSome (AdipoCreERT2/Bbs1fl/fl mice). Interestingly, a significant increase in renal sympathetic nerve activity, measured using multifiber recording in the conscious state, was observed in AdipoCre/Bbs1fl/fl mice on both chow and HFHSD. A significant increase in tail-cuff arterial pressure was also observed in chow-fed AdipoCre/Bbs1fl/fl mice, but this was not reproduced when arterial pressure was measured by radiotelemetry. Moreover, AdipoCre/Bbs1fl/fl mice had no significant alterations in vascular reactivity. On the other hand, AdipoCre/Bbs1fl/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 and sympathetic traffic. The BBSome also contributes to baroreflex sensitivity under HFHSD, but not normal chow.NEW & NOTEWORTHY The current study show how genetic manipulation of fat cells impacts various functions of the body including sensitivity to the hormone insulin.
期刊介绍:
The American Journal of Physiology-Regulatory, Integrative and Comparative Physiology publishes original investigations that illuminate normal or abnormal regulation and integration of physiological mechanisms at all levels of biological organization, ranging from molecules to humans, including clinical investigations. Major areas of emphasis include regulation in genetically modified animals; model organisms; development and tissue plasticity; neurohumoral control of circulation and hypertension; local control of circulation; cardiac and renal integration; thirst and volume, electrolyte homeostasis; glucose homeostasis and energy balance; appetite and obesity; inflammation and cytokines; integrative physiology of pregnancy-parturition-lactation; and thermoregulation and adaptations to exercise and environmental stress.