ArticleMolecular metabolism2020
Deletion of iRhom2 protects against diet-induced obesity by increasing thermogenesis.
Article in Molecular metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 37 citations in OpenAlex.
- ADAM17 and its proteolytic targets in disease pathogenesis.The FEBS journal · 2026Review
- Holding Out for a Model: Rhomboid Superfamily in Vertebrate Development and Disease.Journal of cellular physiology · 2025Review
- Analysis of the function of ADAM17 in iRhom2 curly-bare and tylosis with esophageal cancer mutant mice.Journal of cell science · 2023Article
- iRHOM2 regulates inflammation and endothelial barrier permeability via CX3CL1.Experimental and therapeutic medicine · 2023Article
- Differentiation of Human Pluripotent Stem Cells (hPSCs) into Brown-Like Adipocytes.Methods in molecular biology (Clifton, N.J.) · 2023Article
- iRhom pseudoproteases regulate ER stress-induced cell death through IPNature communications · 2022Article
- The pseudoprotease iRhom1 controls ectodomain shedding of membrane proteins in the nervous system.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Mitochondrial Lipid Homeostasis at the Crossroads of Liver and Heart Diseases.International journal of molecular sciences · 2021Review
- Oxytocin Involvement in Body Composition Unveils the True Identity of Oxytocin.International journal of molecular sciences · 2021Review
- Contribution of ADAM17 and related ADAMs in cardiovascular diseases.Cellular and molecular life sciences : CMLS · 2021Review
- UCP1 regulates ALDH-positive breast cancer stem cells through releasing the suppression of Snail on FBP1.Cell biology and toxicology · 2021Article
- Unraveling the Developmental Roadmap toward Human Brown Adipose Tissue.Stem cell reports · 2021Article
- 4-Hydroxyisoleucine relieves inflammation through iRhom2-dependent pathway in co-cultured macrophages and adipocytes with LPS stimulation.BMC complementary medicine and therapies · 2020Article
- Adipocyte ADAM17 plays a limited role in metabolic inflammation.Adipocyte · 2020Article
- The Role of iRhom2 in Metabolic and Cardiovascular-Related Disorders.Frontiers in cardiovascular medicine · 2020Review
Corrections and comments
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Authors and funding
19 authors at 9 institutions in 5 countries.
Funding
Abstract
objectiveObesity 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.
methodsWe 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.
resultsDeletion 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.
conclusionOur data suggest that iRhom2 is a negative regulator of thermogenesis and plays a role in the control of adipose tissue homeostasis during metabolic disease.
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