Min Hyeonyoung, Yang Yale Y, Yang Yunlei
Department of Medicine, Division of Endocrinology, Albert Einstein College of Medicine, Bronx, United States.
Friends Seminary, New York, United States.
Elife. 2025 Jan 30;13:RP98353. doi: 10.7554/eLife.98353.
It has been well documented that cold is an enhancer of lipid metabolism in peripheral tissues, yet its effect on central nervous system lipid dynamics is underexplored. It is well recognized that cold acclimations enhance adipocyte functions, including white adipose tissue lipid lipolysis and beiging, and brown adipose tissue thermogenesis in mammals. However, it remains unclear whether and how lipid metabolism in the brain is also under the control of ambient temperature. Here, we show that cold exposure predominantly increases the expressions of the lipid lipolysis genes and proteins within the paraventricular nucleus of the hypothalamus (PVH) in male mice. Mechanistically, by using innovatively combined brain-region selective pharmacology and in vivo time-lapse photometry monitoring of lipid metabolism, we find that cold activates cells within the PVH and pharmacological inactivation of cells blunts cold-induced effects on lipid peroxidation, accumulation of lipid droplets, and lipid lipolysis in the PVH. Together, these findings suggest that PVH lipid metabolism is cold sensitive and integral to cold-induced broader regulatory responses.
已有充分文献记载，寒冷是外周组织脂质代谢的增强剂，但其对中枢神经系统脂质动态的影响尚未得到充分研究。众所周知，冷适应可增强哺乳动物的脂肪细胞功能，包括白色脂肪组织脂质脂解和米色化，以及棕色脂肪组织产热。然而，目前尚不清楚大脑中的脂质代谢是否以及如何受环境温度的控制。在这里，我们表明，冷暴露主要增加雄性小鼠下丘脑室旁核（PVH）内脂质脂解基因和蛋白质的表达。从机制上讲，通过创新性地结合脑区选择性药理学和脂质代谢的体内延时光度监测，我们发现寒冷激活了PVH内的细胞，而细胞的药理学失活减弱了寒冷对PVH脂质过氧化、脂滴积累和脂质脂解的影响。总之，这些发现表明PVH脂质代谢对寒冷敏感，并且是寒冷诱导的更广泛调节反应所必需的。
