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Loss of Brain Angiogenesis Inhibitor-3 (BAI3) G-Protein Coupled Receptor in Mice Regulates Adaptive Thermogenesis by Enhancing Energy Expenditure

Authors :
Haifa Alsharif
Mary N. Latimer
Katherine C. Perez
Justin Alexander
Md Mostafizur Rahman
Anil K. Challa
Jeong-A. Kim
Sasanka Ramanadham
Martin Young
Sushant Bhatnagar
Source :
Metabolites, Vol 13, Iss 6, p 711 (2023)
Publication Year :
2023
Publisher :
MDPI AG, 2023.

Abstract

Effective energy expenditure is critical for maintaining body weight (BW). However, underlying mechanisms contributing to increased BW remain unknown. We characterized the role of brain angiogenesis inhibitor-3 (BAI3/ADGRB3), an adhesion G-protein coupled receptor (aGPCR), in regulating BW. A CRISPR/Cas9 gene editing approach was utilized to generate a whole-body deletion of the BAI3 gene (BAI3−/−). In both BAI3−/− male and female mice, a significant reduction in BW was observed compared to BAI3+/+ control mice. Quantitative magnetic imaging analysis showed that lean and fat masses were reduced in male and female mice with BAI3 deficiency. Total activity, food intake, energy expenditure (EE), and respiratory exchange ratio (RER) were assessed in mice housed at room temperature using a Comprehensive Lab Animal Monitoring System (CLAMS). While no differences were observed in the activity between the two genotypes in male or female mice, energy expenditure was increased in both sexes with BAI3 deficiency. However, at thermoneutrality (30 °C), no differences in energy expenditure were observed between the two genotypes for either sex, suggesting a role for BAI3 in adaptive thermogenesis. Notably, in male BAI3−/− mice, food intake was reduced, and RER was increased, but these attributes remained unchanged in the female mice upon BAI3 loss. Gene expression analysis showed increased mRNA abundance of thermogenic genes Ucp1, Pgc1α, Prdm16, and Elov3 in brown adipose tissue (BAT). These outcomes suggest that adaptive thermogenesis due to enhanced BAT activity contributes to increased energy expenditure and reduced BW with BAI3 deficiency. Additionally, sex-dependent differences were observed in food intake and RER. These studies identify BAI3 as a novel regulator of BW that can be potentially targeted to improve whole-body energy expenditure.

Details

Language :
English
ISSN :
22181989
Volume :
13
Issue :
6
Database :
Directory of Open Access Journals
Journal :
Metabolites
Publication Type :
Academic Journal
Accession number :
edsdoj.6db45d1f199a4eb3b7390d521cd46ac2
Document Type :
article
Full Text :
https://doi.org/10.3390/metabo13060711