Ontology highlight
ABSTRACT: Objective
Obesity is the result of positive energy balance. It can be caused by excessive energy consumption but also by decreased energy dissipation, which occurs under several conditions including when the development or activation of brown adipose tissue (BAT) is impaired. Here we evaluated whether iRhom2, the essential cofactor for the Tumour Necrosis Factor (TNF) sheddase ADAM17/TACE, plays a role in the pathophysiology of metabolic syndrome.Methods
We challenged WT versus iRhom2 KO mice to positive energy balance by chronic exposure to a high fat diet and then compared their metabolic phenotypes. We also carried out ex vivo assays with primary and immortalized mouse brown adipocytes to establish the autonomy of the effect of loss of iRhom2 on thermogenesis and respiration.Results
Deletion of iRhom2 protected mice from weight gain, dyslipidemia, adipose tissue inflammation, and hepatic steatosis and improved insulin sensitivity when challenged by a high fat diet. Crucially, the loss of iRhom2 promotes thermogenesis via BAT activation and beige adipocyte recruitment, enabling iRhom2 KO mice to dissipate excess energy more efficiently than WT animals. This effect on enhanced thermogenesis is cell-autonomous in brown adipocytes as iRhom2 KOs exhibit elevated UCP1 levels and increased mitochondrial proton leak.Conclusion
Our data suggest that iRhom2 is a negative regulator of thermogenesis and plays a role in the control of adipose tissue homeostasis during metabolic disease.
SUBMITTER: Badenes M
PROVIDER: S-EPMC6909339 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Badenes Marina M Amin Abdulbasit A González-García Ismael I Félix Inês I Burbridge Emma E Cavadas Miguel M Ortega Francisco José FJ de Carvalho Érika É Faísca Pedro P Carobbio Stefania S Seixas Elsa E Pedroso Dora D Neves-Costa Ana A Moita Luís F LF Fernández-Real José Manuel JM Vidal-Puig António A Domingos Ana A López Miguel M Adrain Colin C
Molecular metabolism 20191031
<h4>Objective</h4>Obesity is the result of positive energy balance. It can be caused by excessive energy consumption but also by decreased energy dissipation, which occurs under several conditions including when the development or activation of brown adipose tissue (BAT) is impaired. Here we evaluated whether iRhom2, the essential cofactor for the Tumour Necrosis Factor (TNF) sheddase ADAM17/TACE, plays a role in the pathophysiology of metabolic syndrome.<h4>Methods</h4>We challenged WT versus i ...[more]