Endothelial BBSome is essential for vascular, metabolic, and retinal functions. Mol Metab 2021 Nov;53:101308
Date
07/26/2021Pubmed ID
34303879Pubmed Central ID
PMC8379702DOI
10.1016/j.molmet.2021.101308Scopus ID
2-s2.0-85113702369 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
OBJECTIVES: Endothelial cells that line the entire vascular system play a pivotal role in the control of various physiological processes, including metabolism. Additionally, endothelial dysfunction is associated with many pathological conditions, including obesity. Here, we assessed the role of the BBSome, a protein complex composed of eight Bardet-Biedl syndrome (BBS) proteins in endothelial cells.
METHODS: We studied the effects of BBSome disruption in endothelial cells on vascular function, body weight, glucose homeostasis, and the liver and retina. For this, we generated mice with selective BBSome disruption in endothelial cells through Bbs1 gene deletion.
RESULTS: We found that endothelial cell-specific BBSome disruption causes endothelial dysfunction, as indicated by the impaired acetylcholine-induced vasorelaxation in both the aorta and mesenteric artery. This was associated with an increase in the contractile response to thromboxane A2 receptor agonist (U46619) in the mesenteric artery. Mechanistically, we demonstrated that mice lacking the Bbs1 gene in endothelial cells show elevated vascular angiotensinogen gene expression, implicating renin-angiotensin system activation in the vascular changes evoked by endothelial BBSome deficiency. Strikingly, our data indicate that endothelial BBSome deficiency increases body weight and fat mass and causes hepatosteatosis along with alterations in hepatic expression of lipid metabolism-related genes and metabolomics profile. In addition, electroretinogram and optical coherence tomography analyses revealed functional and structural abnormalities in the retina, evoked by absence of the endothelial BBSome.
CONCLUSIONS: Our findings demonstrate that the BBSome in endothelial cells is required for the regulation of vascular function, adiposity, hepatic lipid metabolism, and retinal function.
Author List
Jiang J, Reho JJ, Bhattarai S, Cherascu I, Hedberg-Buenz A, Meyer KJ, Tayyari F, Rauckhorst AJ, Guo DF, Morgan DA, Taylor EB, Anderson MG, Drack AV, Rahmouni KAuthor
John J. Reho Research Scientist II in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBody Weight
Endothelial Cells
Female
Male
Mice
Mice, Congenic
Mice, Inbred C57BL
Mice, Transgenic
Microtubule-Associated Proteins
Retina
