Cold Exposure Promotes Atherosclerotic Plaque Growth and Instability via UCP1-Dependent Lipolysis
2013 (English)In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 18, no 1, 118-129 p.Article in journal (Refereed) Published
Molecular mechanisms underlying the cold-associated high cardiovascular risk remain unknown. Here, we show that the cold-triggered food-intake-independent lipolysis significantly increased plasma levels of small low-density lipoprotein (LDL) remnants, leading to accelerated development of atherosclerotic lesions in mice. In two genetic mouse knockout models (apolipoprotein E-/- [ApoE(-/-)] and LDL receptor(-/-) [Ldlr(-/-)] mice), persistent cold exposure stimulated atherosclerotic plaque growth by increasing lipid deposition. Furthermore, marked increase of inflammatory cells and plaque-associated microvessels were detected in the cold-acclimated ApoE(-/-) and Ldlr(-/-) mice, leading to plaque instability. Deletion of uncoupling protein 1 (UCP1), a key mitochondrial protein involved in thermogenesis in brown adipose tissue (BAT), in the ApoE(-/-) strain completely protected mice from the cold-induced atherosclerotic lesions. Cold acclimation markedly reduced plasma levels of adiponectin, and systemic delivery of adiponectin protected ApoE(-/-) mice from plaque development. These findings provide mechanistic insights on low-temperature-associated cardiovascular risks.
Place, publisher, year, edition, pages
Elsevier (Cell Press) , 2013. Vol. 18, no 1, 118-129 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-101394DOI: 10.1016/j.cmet.2013.06.003ISI: 000326267100015OAI: oai:DiVA.org:liu-101394DiVA: diva2:666295
Funding Agencies|Swedish Research Council||Swedish Cancer Foundation||Karolinska Institute Foundation||Karolinska Institute Distinguished Professor Award||Torsten Soderbergs Foundation||Tianjin Natural Science Foundation (CMM-Tianjin)|09ZCZDSF04400|ImClone Systems of Eli Lilly||European Union Integrated Project of Metoxia|222741|European Research Council (ERC) advanced grant ANGIOFAT|250021|National 973 Basic Research Program of China|2011CB5039062012CB518603|National High-Tech Research and Development Program of China|2012AA02A510|Program of Introducing Talents of Discipline to Universities|B07035|State Program of National Natural Science Foundation of China for Innovative Research Group|81021001|National Natural Science Foundation of China|811002078117325181100102812703508100012681000127|2013-11-222013-11-212014-09-11