Loss of iRhom2 accelerates fat gain and insulin resistance in diet-induced obesity despite reduced adipose tissue inflammation.

Metabolism: Clinical and Experimental
Joseph SkurskiThorsten Maretzky

Abstract

Low-grade inflammation and metabolic dysregulation are common comorbidities of obesity, both of which are associated with alterations in iRhom2-regulated pro-inflammatory cytokine and epidermal growth factor receptor (EGFR) ligand signaling. Our objective was to determine the role of iRhom2 in the regulation of low-grade inflammation and metabolic dysregulation in a murine model of diet-induced obesity. Wild type (WT) and iRhom2-deficient mice were fed normal chow (NC) or a high-fat diet (HFD) starting at 5 weeks of age for up to 33 weeks. Body composition, glucose and insulin tolerance, feeding behavior, and indirect calorimetry were measured at defined time points. Adipose tissue cytokine expression and inflammatory lesions known as crown-like structures (CLS) were analyzed at the end-point of the study. iRhom2-deficient mice show accelerated fat gain on a HFD, accompanied by insulin resistance. Indirect calorimetry did not demonstrate changes in energy expenditure or food intake, but locomotor activity was significantly reduced in HFD iRhom2-deficient mice. Interestingly, CLS, macrophage infiltration, and tumor necrosis factor (TNF) production were decreased in adipose tissue from HFD iRhom2-deficient mice, but circulating c...Continue Reading

Citations

Sep 8, 2020·The FEBS Journal·Colin Adrain, Miguel Cavadas
Sep 8, 2020·Adipocyte·Joseph C LownikRebecca K Martin
Dec 18, 2020·Frontiers in Cardiovascular Medicine·Ramasatyaveni GeesalaThorsten Maretzky
Oct 21, 2020·The Journal of Investigative Dermatology·Jennifer Chao-ChuDavid P Kelsell
Jun 17, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ahmed K AladhamiReilly T Enos
Oct 7, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Johanna TüshausStefan F Lichtenthaler

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