Jesse W Williams1, Andrew Elvington1, Stoyan Ivanov1, Skyler Kessler1, Hannah Luehmann1, Osamu Baba1, Brian T Saunders1, Ki-Wook Kim1, Michael W Johnson1, Clarissa S Craft1, Jae-Hoon Choi1, Mary G Sorci-Thomas1, Bernd H Zinselmeyer1, Jonathan R Brestoff1, Yongjian Liu1, Gwendalyn J Randolph2. 1. From the Department of Pathology and Immunology (J.W.W., A.E., S.I., S.K., O.B., B.T.S., K.-W.K., M.W.J., J.-H.C., B.H.Z., J.R.B., G.J.R.), Department of Radiology (H.L., Y.L.), and Department of Medicine, Division of Bone and Mineral Diseases (C.S.C.), Washington University School of Medicine, St. Louis, MO; Division of Health and Sport Sciences, Missouri Baptist University, St. Louis (A.E.); Department of Life Science, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul, South Korea (J.-H.C.); and Department of Medicine, Division of Endocrinology, Medical College of Wisconsin, Milwaukee (M.G.S.-T.). 2. From the Department of Pathology and Immunology (J.W.W., A.E., S.I., S.K., O.B., B.T.S., K.-W.K., M.W.J., J.-H.C., B.H.Z., J.R.B., G.J.R.), Department of Radiology (H.L., Y.L.), and Department of Medicine, Division of Bone and Mineral Diseases (C.S.C.), Washington University School of Medicine, St. Louis, MO; Division of Health and Sport Sciences, Missouri Baptist University, St. Louis (A.E.); Department of Life Science, College of Natural Sciences, Research Institute for Natural Sciences, Hanyang University, Seoul, South Korea (J.-H.C.); and Department of Medicine, Division of Endocrinology, Medical College of Wisconsin, Milwaukee (M.G.S.-T.). gjrandolph@wustl.edu.
Abstract
RATIONALE: Ambient temperature is a risk factor for cardiovascular disease. Cold weather increases cardiovascular events, but paradoxically, cold exposure is metabolically protective because of UCP1 (uncoupling protein 1)-dependent thermogenesis. OBJECTIVE: We sought to determine the differential effects of ambient environmental temperature challenge and UCP1 activation in relation to cardiovascular disease progression. METHODS AND RESULTS: Using mouse models of atherosclerosis housed at 3 different ambient temperatures, we observed that cold temperature enhanced, whereas thermoneutral housing temperature inhibited atherosclerotic plaque growth, as did deficiency in UCP1. However, whereas UCP1 deficiency promoted poor glucose tolerance, thermoneutral housing enhanced glucose tolerance, and this effect held even in the context of UCP1 deficiency. In conditions of thermoneutrality, but not UCP1 deficiency, circulating monocyte counts were reduced, likely accounting for fewer monocytes entering plaques. Reductions in circulating blood monocytes were also found in a large human cohort in correlation with environmental temperature. By contrast, reduced plaque growth in mice lacking UCP1 was linked to lower cholesterol. Through application of a positron emission tomographic tracer to track CCR2+ cell localization and intravital 2-photon imaging of bone marrow, we associated thermoneutrality with an increased monocyte retention in bone marrow. Pharmacological activation of β3-adrenergic receptors applied to mice housed at thermoneutrality induced UCP1 in beige fat pads but failed to promote monocyte egress from the marrow. CONCLUSIONS: Warm ambient temperature is, like UCP1 deficiency, atheroprotective, but the mechanisms of action differ. Thermoneutrality associates with reduced monocyte egress from the bone marrow in a UCP1-dependent manner in mice and likewise may also suppress blood monocyte counts in man.
RATIONALE: Ambient temperature is a risk factor for cardiovascular disease. Cold weather increases cardiovascular events, but paradoxically, cold exposure is metabolically protective because of UCP1 (uncoupling protein 1)-dependent thermogenesis. OBJECTIVE: We sought to determine the differential effects of ambient environmental temperature challenge and UCP1 activation in relation to cardiovascular disease progression. METHODS AND RESULTS: Using mouse models of atherosclerosis housed at 3 different ambient temperatures, we observed that cold temperature enhanced, whereas thermoneutral housing temperature inhibited atherosclerotic plaque growth, as did deficiency in UCP1. However, whereas UCP1 deficiency promoted poor glucose tolerance, thermoneutral housing enhanced glucose tolerance, and this effect held even in the context of UCP1 deficiency. In conditions of thermoneutrality, but not UCP1 deficiency, circulating monocyte counts were reduced, likely accounting for fewer monocytes entering plaques. Reductions in circulating blood monocytes were also found in a large human cohort in correlation with environmental temperature. By contrast, reduced plaque growth in mice lacking UCP1 was linked to lower cholesterol. Through application of a positron emission tomographic tracer to track CCR2+ cell localization and intravital 2-photon imaging of bone marrow, we associated thermoneutrality with an increased monocyte retention in bone marrow. Pharmacological activation of β3-adrenergic receptors applied to mice housed at thermoneutrality induced UCP1 in beige fat pads but failed to promote monocyte egress from the marrow. CONCLUSIONS: Warm ambient temperature is, like UCP1 deficiency, atheroprotective, but the mechanisms of action differ. Thermoneutrality associates with reduced monocyte egress from the bone marrow in a UCP1-dependent manner in mice and likewise may also suppress blood monocyte counts in man.
Authors: Khurram Nasir; Eliseo Guallar; Ana Navas-Acien; Michael H Criqui; João A C Lima Journal: Arterioscler Thromb Vasc Biol Date: 2005-06-23 Impact factor: 8.311
Authors: Alexander Bartelt; Oliver T Bruns; Rudolph Reimer; Heinz Hohenberg; Harald Ittrich; Kersten Peldschus; Michael G Kaul; Ulrich I Tromsdorf; Horst Weller; Christian Waurisch; Alexander Eychmüller; Philip L S M Gordts; Franz Rinninger; Karoline Bruegelmann; Barbara Freund; Peter Nielsen; Martin Merkel; Joerg Heeren Journal: Nat Med Date: 2011-01-23 Impact factor: 53.440
Authors: Orit Jacobson; Ido D Weiss; Lawrence Szajek; Joshua M Farber; Dale O Kiesewetter Journal: Bioorg Med Chem Date: 2009-01-15 Impact factor: 3.641
Authors: Wouter D van Marken Lichtenbelt; Joost W Vanhommerig; Nanda M Smulders; Jamie M A F L Drossaerts; Gerrit J Kemerink; Nicole D Bouvy; Patrick Schrauwen; G J Jaap Teule Journal: N Engl J Med Date: 2009-04-09 Impact factor: 91.245
Authors: R T Palframan; S Jung; G Cheng; W Weninger; Y Luo; M Dorf; D R Littman; B J Rollins; H Zweerink; A Rot; U H von Andrian Journal: J Exp Med Date: 2001-11-05 Impact factor: 14.307
Authors: Wenjun Li; Hannah P Luehmann; Hsi-Min Hsiao; Satona Tanaka; Ryuji Higashikubo; Jason M Gauthier; Deborah Sultan; Kory J Lavine; Steven L Brody; Andrew E Gelman; Robert J Gropler; Yongjian Liu; Daniel Kreisel Journal: Arterioscler Thromb Vasc Biol Date: 2018-03-22 Impact factor: 8.311