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寒冷刺激调控小鼠脂质代谢和皮下脂肪外泌体分泌

柯烁¹, 徐莉², 史瑞雪¹, 王佳琦¹, 崔乐¹, 纪元¹, 李菁¹, 姜晓宏^1,*

¹南京大学生命科学学院，南京 210023；²南京大学医学院附属鼓楼医院，南京 210008

摘要

寒冷是哺乳动物进化过程中长期面临的生存挑战。在寒冷应激情况下，除褐色脂肪通过吸收糖脂产热维持体温外，寒冷刺激也能激活皮下米色脂肪的产热功能。但是，寒冷应激对其他组织和全身脂代谢的影响尚不明确。我们前期的研究表明在寒冷应激情况下，褐色脂肪组织除自身产热外，还可以通过分泌大量的外泌体介导组织器官间的信息交互，但皮下脂肪是否具有类似的机制尚不清楚。本研究旨在探索冷刺激下不同组织的脂代谢变化，以及皮下脂肪是否通过外泌体调控全身糖脂代谢，以深入理解生理应激下的脂代谢稳态调节机制。采用RT-qPCR、Western blot及H&E染色等方法，探究小鼠在冷刺激下血清、肝脏、附睾白色脂肪，皮下脂肪脂质代谢的生理性变化。结果显示在冷刺激下皮下脂肪表现出显著的产热活性，外泌体分泌显著增加，且这些外泌体能被肝细胞摄取，显著影响肝细胞脂代谢，表现为脂质合成和分解途径关键基因表达水平的变化。本研究揭示了在冷刺激下皮下脂肪通过外泌体调控脂代谢的新机制，为理解米色脂肪在寒冷应激下的系统调控作用提供了新见解，也为开发肥胖和代谢性疾病的新治疗策略提供了理论基础。

关键词： 皮下脂肪组织; 冷暴露; 脂质代谢; 外泌体

Cold stimulation regulates lipid metabolism and the secretion of exosomes from subcutaneous adipose tissue in mice

KE Shuo¹, XU Li², SHI Rui-Xue¹, WANG Jia-Qi¹, CUI Le¹, JI Yuan¹, LI Jing¹, JIANG Xiao-Hong^1,*

¹School of Life Sciences, Nanjing University, Nanjing 210023, China；²Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, China

Abstract

Cold has been a long-term survival challenge in the evolutionary process of mammals. In response to cold stress, in addition to brown adipose tissue (BAT) dissipating energy as heat through glucose and lipid oxidation to maintain body temperature, cold stimulation can strongly activate thermogenesis and energy expenditure in beige fat cells, which are widely distributed in the subcutaneous layer. However, the effects of cold stimulation on other tissues and systemic lipid metabolism remain unclear. Our previous research indicated that, under cold stress, BAT not only produces heat but also secretes numerous exosomes to mediate BAT-liver crosstalk. Whether subcutaneous fat has a similar mechanism is still unknown. Therefore, this study aimed to investigate the alterations in lipid metabolism across various tissues under cold exposure and to explore whether subcutaneous fat regulates systemic glucose and lipid metabolism via exosomes, thereby elucidating the regulatory mechanisms of lipid metabolism homeostasis under physiological stress. RT-qPCR, Western blot, and H&E staining methods were used to investigate the physiological changes in lipid metabolism in the serum, liver, epididymal white adipose tissue, and subcutaneous fat of mice under cold stimulation. The results revealed that cold exposure significantly enhanced the thermogenic activity of subcutaneous adipose tissue and markedly increased exosome secretion. These exosomes were efficiently taken up by hepatocytes, where they profoundly influenced hepatic lipid metabolism, as evidenced by alterations in the expression levels of key genes involved in lipid synthesis and catabolism pathways. This study has unveiled a novel mechanism by which subcutaneous fat regulates lipid metabolism through exosome secretion under cold stimulation, providing new insights into the systemic regulatory role of beige adipocytes under cold stress and offering a theoretical basis for the development of new therapeutic strategies for obesity and metabolic diseases. 

Key words: subcutaneous adipose tissue; cold exposure; lipid metabolism; exosomes

收稿日期：　　录用日期：

通讯作者：姜晓宏　　E-mail:

DOI: 10.13294/j.aps.2025.0022

引用本文：

柯烁, 徐莉, 史瑞雪, 王佳琦, 崔乐, 纪元, 李菁, 姜晓宏. 寒冷刺激调控小鼠脂质代谢和皮下脂肪外泌体分泌[J]. 生理学报 2025; 77 (2): 231-240.

KE Shuo, XU Li, SHI Rui-Xue, WANG Jia-Qi, CUI Le, JI Yuan, LI Jing, JIANG Xiao-Hong. Cold stimulation regulates lipid metabolism and the secretion of exosomes from subcutaneous adipose tissue in mice. Acta Physiol Sin 2025; 77 (2): 231-240 (in Chinese with English abstract).