title: Thermoneutral Housing Accelerates Metabolic Inflammation to Potentiate Atherosclerosis but Not Insulin Resistance.
abstract: Chronic, low-grade inflammation triggered by excess intake of dietary lipids has been proposed to contribute to the pathogenesis of metabolic disorders, such as obesity, insulin resistance, type 2 diabetes, and atherosclerosis. Although considerable evidence supports a causal association between inflammation and metabolic diseases, most tests of this link have been performed in cold-stressed mice that are housed below their thermoneutral zone. We report here that thermoneutral housing of mice has a profound effect on the development of metabolic inflammation, insulin resistance, and atherosclerosis. Mice housed at thermoneutrality develop metabolic inflammation in adipose tissue and in the vasculature at an accelerated rate. Unexpectedly, this increased inflammatory response contributes to the progression of atherosclerosis but not insulin resistance. These findings not only suggest that metabolic inflammation can be uncoupled from obesity-associated insulin resistance, but also point to how thermal stress might limit our ability to faithfully model human diseases in mice.
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Xiao Yu
authors.initials: XY
authors.lastname: Tian
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Kirthana
authors.initials: K
authors.lastname: Ganeshan
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hong
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Khoa D
authors.initials: KD
authors.lastname: Nguyen
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Yifu
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Rajendra K
authors.initials: RK
authors.lastname: Tangirala
authors.forename: Peter
authors.initials: P
authors.lastname: Tontonoz
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA; Howard Hughes Medical Institute, University of California Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Tonotonoz
authors.affiliation: Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94143, USA; Departments of Physiology and Medicine, University of California San Francisco, San Francisco, CA 94143, USA. Electronic address: ajay.chawla@ucsf.edu.
authors.forename: Ajay
authors.initials: A
authors.lastname: Chawla
mesh_terms: D056704:Adaptive Immunity; D052436:Adipose Tissue, White / Q000276:immunology / Q000473:pathology; D000818:Animals; D001013:Aorta, Thoracic / Q000276:immunology / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology / Q000276:immunology*; D059305:Diet, High-Fat / Q000009:adverse effects; D004781:Environmental Exposure; D006799:Housing, Animal; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology; D007333:Insulin Resistance / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
chemical_list: D001057:Apolipoproteins E