Cold Exposure Promotes Atherosclerotic Plaque Growth and Instability via UCP1-Dependent Lipolysis

• DOI: 10.1016/j.cmet.2013.06.003
• Publication Date: 2013-07-02T15:44:08Z
• Authors: Mei Dong; Xiaoyan Yang; Sharon Lim; Ziquan Cao; Jennifer Honek; Huixia Lu; Cheng Zhang; Takahiro Seki; Kayoko Hosaka; Eric Wahlberg; Jianmin Yang; Lei Zhang; Toste Länne; Baocun Sun; Xuri Li; Yizhi Liu; Yun Zhang; Yihai Cao
• Keywords: Adult; Male; Medicin och hälsovetenskap; Physiology; Acclimatization; Lipolysis; Medical and Health Sciences; Ion Channels; Mitochondrial Proteins; Mice; 03 medical and health sciences; Short Article; Apolipoproteins E; Adipose Tissue, Brown; Animals; Humans; Molecular Biology; Mice, Knockout; 0303 health sciences; Cell Biology; Cholesterol, LDL; Middle Aged; Atherosclerosis; Lipid Metabolism; Cold Temperature; Disease Models, Animal; Female; Adiponectin

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.