biostudies-literatureAmin AMedical Research Council101731https://www.ebi.ac.uk/biostudies/studies/S-EPMC10197113biostudies-literatureUnknown73<h4>Objective</h4>The metalloprotease ADAM17 (also called TACE) plays fundamental roles in homeostasis by shedding key signaling molecules from the cell surface. Although its importance for the immune system and epithelial tissues is well-documented, little is known about the role of ADAM17 in metabolic homeostasis. The purpose of this study was to determine the impact of ADAM17 expression, specifically in adipose tissues, on metabolic homeostasis.<h4>Methods</h4>We used histopathology, molecular, proteomic, transcriptomic, in vivo integrative physiological and ex vivo biochemical approaches to determine the impact of adipose tissue-specific deletion of ADAM17 upon adipocyte and whole organism metabolic physiology.<h4>Results</h4>ADAM17^{adipoq-creΔ/Δ} mice exhibited a hypermetabolMolecular metabolismSemaphorin 4B is an ADAM17-cleaved adipokine that inhibits adipocyte differentiation and thermogenesis.PMC10197113MC_UU_00014/5MC_UU_00014/2Maguire STushaus JVidal-Puig ACarobbio Sde Carvalho EBarros AMoita LFFaisca PAmin ADomingos PMLichtenthaler SFFernandez-Real JMBadenes MBurbridge EAdrain CStrisovsky KTravnickova KOrtega FJfalseSemaphorin 4B is an ADAM17-cleaved adipokine that inhibits adipocyte differentiation and thermogenesis.<h4>Objective</h4>The metalloprotease ADAM17 (also called TACE) plays fundamental roles in homeostasis by shedding key signaling molecules from the cell surface. Although its importance for the immune system and epithelial tissues is well-documented, little is known about the role of ADAM17 in metabolic homeostasis. The purpose of this study was to determine the impact of ADAM17 expression, specifically in adipose tissues, on metabolic homeostasis.<h4>Methods</h4>We used histopathology, molecular, proteomic, transcriptomic, in vivo integrative physiological and ex vivo biochemical approaches to determine the impact of adipose tissue-specific deletion of ADAM17 upon adipocyte and whole organism metabolic physiology.<h4>Results</h4>ADAM17^{adipoq-creΔ/Δ} mice exhibited a hypermetabol2023-01-01T00:00:00Z2023 Jul2026-06-23T03:25:38.534Z2025-02-19T04:44:11.01ZS-EPMC101971133712150910.1016/j.molmet.2023.101731