Endothelial BBSome is Essential for Vascular, Metabolic, and Retinal Functions

Jingwei Jiang; John J Reho; Sajag Bhattarai; Ioana Cherascu; Adam Hedberg-Buenz; Kacie J Meyer; Fariba Tayyari; Adam J Rauckhorst; Deng Fu Guo; Donald A Morgan; Eric B Taylor; Michael G Anderson; Arlene V Drack; Kamal Rahmouni

doi:10.1016/j.molmet.2021.101308

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Endothelial BBSome is Essential for Vascular, Metabolic, and Retinal Functions

Journal article

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Endothelial BBSome is Essential for Vascular, Metabolic, and Retinal Functions

Jingwei Jiang, John J Reho, Sajag Bhattarai, Ioana Cherascu, Adam Hedberg-Buenz, Kacie J Meyer, Fariba Tayyari, Adam J Rauckhorst, Deng Fu Guo, Donald A Morgan, …

Molecular metabolism (Germany), Vol.53, 101308

07/22/2021

DOI: 10.1016/j.molmet.2021.101308

PMCID: PMC8379702

PMID: 34303879

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Abstract

– Endothelial cells that line the entire vascular system play a pivotal role in the control of various physiological processes including metabolism. Moreover, 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 including BBS1, in endothelial cells. –We studied the effects of BBSome disruption in endothelial cells on vascular function, body weight, glucose homeostasis, liver and retina. For this, we generated mice bearing selective BBSome disruption, through Bbs1 gene deletion, in endothelial cells. – 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 contractile response to thromboxane A2 receptor agonist (U46619) in the mesenteric artery. Mechanistically, we show that mice lacking the Bbs1 gene in endothelial cells have elevated vascular angiotensinogen gene expression implicating the renin-angiotensin system activation in the vascular changes evoked by endothelial BBSome deficiency. Strikingly, our data indicate that endothelial BBSome deficiency increase body weight and fat mass and causes hepatosteatosis along with alterations in hepatic expression of lipid metabolism–related genes and metabolomics profile. Moreover, electroretinogram and optical coherence tomography analyses revealed functional and structural abnormalities in the retina evoked by absence of the endothelial BBSome. – Our findings demonstrate that the BBSome in endothelial cells is required for the regulation of vascular function, adiposity, hepatic lipid metabolism, and retinal function. [Display omitted] •Disruption of the BBSome in endothelial cells alter vascular reactivity.•Loss of the BBSome in endothelial cells increases vascular angiotensinogen gene expression.•Endothelial BBSome deficiency increases body weight and fat mass and causes hepatosteatosis.•Absence of the endothelial BBSome evokes functional and structural abnormalities in the retina.

endothelial function

body weight

liver steatosis

retina

BBSome

Details

Title: Subtitle: Endothelial BBSome is Essential for Vascular, Metabolic, and Retinal Functions
Creators: Jingwei Jiang - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
John J Reho - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Sajag Bhattarai - Department of Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Ioana Cherascu - Department of Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Adam Hedberg-Buenz - Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Kacie J Meyer - Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Fariba Tayyari - Metabolomics Core Facility, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
Adam J Rauckhorst - Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Deng Fu Guo - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Donald A Morgan - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Eric B Taylor - Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Michael G Anderson - Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Arlene V Drack - Department of Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Kamal Rahmouni - Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Molecular metabolism (Germany), Vol.53, 101308
DOI: 10.1016/j.molmet.2021.101308
PMID: 34303879
PMCID: PMC8379702
NLM abbreviation: Mol Metab
ISSN: 2212-8778
eISSN: 2212-8778
Publisher: Elsevier GmbH
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health
Language: English
Date published: 07/22/2021
Academic Unit: Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Internal Medicine; Ophthalmology and Visual Sciences
Record Identifier: 9984112334502771

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