Loss of the ciliary gene Bbs4 results in defective thermogenesis due to metabolic inefficiency and impaired lipid metabolism
- Adipose tissue is central to the regulation of energy balance. While white adipose tissue (WAT) is responsible for triglyceride storage, brown adipose tissue specializes in energy expenditure. Deterioration of brown adipocyte function contributes to the development of metabolic complications like obesity and diabetes. These disorders are also leading symptoms of the Bardet-Biedl syndrome (BBS), a hereditary disorder in humans which is caused by dysfunctions of the primary cilium and which therefore belongs to the group of ciliopathies. The cilium is a hair-like organelle involved in cellular signal transduction. The BBSome, a supercomplex of several Bbs gene products, localizes to the basal body of cilia and is thought to be involved in protein sorting to and from the ciliary membrane. The effects of a functional BBSome on energy metabolism and lipid mobilization in brown and white adipocytes were tested in whole-body Bbs4 knockout mice that were subjected to metabolic challenges. Chronic cold exposure reveals cold-intolerance ofAdipose tissue is central to the regulation of energy balance. While white adipose tissue (WAT) is responsible for triglyceride storage, brown adipose tissue specializes in energy expenditure. Deterioration of brown adipocyte function contributes to the development of metabolic complications like obesity and diabetes. These disorders are also leading symptoms of the Bardet-Biedl syndrome (BBS), a hereditary disorder in humans which is caused by dysfunctions of the primary cilium and which therefore belongs to the group of ciliopathies. The cilium is a hair-like organelle involved in cellular signal transduction. The BBSome, a supercomplex of several Bbs gene products, localizes to the basal body of cilia and is thought to be involved in protein sorting to and from the ciliary membrane. The effects of a functional BBSome on energy metabolism and lipid mobilization in brown and white adipocytes were tested in whole-body Bbs4 knockout mice that were subjected to metabolic challenges. Chronic cold exposure reveals cold-intolerance of knockout mice but also ameliorates the markers of metabolic pathology detected in knockouts prior to cold. Hepatic triglyceride content is markedly reduced in knockout mice while circulating lipids are elevated, altogether suggesting that defective lipid metabolism in adipose tissue creates increased demand for systemic lipid mobilization to meet energetic demands of reduced body temperatures. These findings taken together suggest that Bbs4 is essential for the regulation of adipose tissue lipid metabolism, representing a potential target to treat metabolic disorders.…
Author details: | Sabrina GohlkeORCiDGND, Carola ManciniORCiD, Francisco Garcia-CarrizoORCiD, Tim J. SchulzORCiDGND |
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DOI: | https://doi.org/10.1096/fj.202100772RR |
ISSN: | 1530-6860 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/34624148 |
Title of parent work (English): | The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology |
Publisher: | Wiley |
Place of publishing: | Hoboken |
Publication type: | Article |
Language: | English |
Date of first publication: | 2021/10/08 |
Publication year: | 2021 |
Release date: | 2023/11/13 |
Tag: | BBsome; Bbs4; adipose tissue; browning; cilium; lipid metabolism |
Volume: | 35 |
Issue: | 11 |
Article number: | e21966 |
Number of pages: | 13 |
Funding institution: | Deutsche Forschungsgemeinschaft (DFG)German Research Foundation (DFG) [2445/5-1, 2445/2-1]; Bundesministerium fur Bildung und Forschung (BMBF)Federal Ministry of Education & Research (BMBF); Paul--Ehrlich-Stiftung; Deutsches Zentrum fur Diabetesforschung DZD [82DZD00302, 82DZD0042G, 82DZD03C3G, 82DZD03D03] |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
DDC classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Peer review: | Referiert |
Publishing method: | Open Access / Hybrid Open-Access |
License (German): | CC-BY-NC - Namensnennung, nicht kommerziell 4.0 International |