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生酮饮食通过上调肝脏和棕色脂肪组织PPARα提高小鼠耐低温能力

李宸涵^1,2, 张伟^1,2, 王盼盼^1,2, 张鹏飞², 安冏², 杨红燕², 高峰², 武桂铃², 张星^2,*

¹西北大学生命科学学院，西安 710069；²中国人民解放军空军军医大学航空航天医学系，教育部航空航天医学重点实验室，西安 710032

摘要

本文旨在探究短期生酮饮食对小鼠耐低温能力的影响及过氧化物酶体增殖物激活受体α (peroxisome proliferator-activated receptor α, PPARα)在其中的作用及机制。将C57BL/6J小鼠分为正常饮食(WT+ND)组与生酮饮食(WT+KD)组，室温下分别用正常或生酮饮食饲料喂养2 d后，将其置于4 °C环境中12 h，检测小鼠在低温条件下核心温度、血糖、血压的变化，并用Western blot检测PPARα和线粒体解偶联蛋白1 (uncoupling protein 1, UCP1)蛋白表达水平。将PPARα敲除小鼠分为正常饮食(PPARα−/−+ND)组与生酮饮食(PPARα−/−+KD)组，室温下分别用正常或生酮饮食饲料喂养2 d后，将其置于4 °C环境中12 h，同样进行上述指标检测。结果显示，在室温下，与WT+ND组相比，WT+KD组小鼠肝脏及棕色脂肪组织中PPARα和UCP1蛋白水平均显著上调。在低温条件下，与WT+ND相比，WT+KD组小鼠核心温度及血糖升高，平均动脉压降低；生酮饮食可上调WT+KD组小鼠棕色脂肪组织中PPARα蛋白表达水平，以及肝脏和棕色脂肪组织中UCP1蛋白表达水平。在低温条件下，与WT+ND组相比，PPARα−/−+ND组小鼠核心温度显著降低，肝脏、骨骼肌、白色和棕色脂肪组织中PPARα和UCP1蛋白表达水平均显著下调；与PPARα−/−+ND组相比，PPARα−/−+KD组小鼠核心温度显著降低，肝脏、骨骼肌、白色和棕色脂肪组织UCP1蛋白水平表达无明显变化。以上结果提示，生酮饮食可能通过上调PPARα表达促进UCP1表达，进而提高小鼠耐低温能力，因此短期生酮饮食可以作为提高机体耐低温能力的潜在干预手段。

关键词： 生酮饮食; 耐低温; 过氧化物酶体增殖物激活受体α

Ketogenic diet improves low temperature tolerance in mice by up-regulating PPARα in the liver and brown adipose tissue

LI Chen-Han^1,2, ZHANG Wei^1,2, WANG Pan-Pan^1,2, ZHANG Peng-Fei², AN Jiong², YANG Hong-Yan², GAO Feng², WU Gui-Ling², ZHANG Xing^2,*

¹College of Life Sciences, Northwest University, Xi’an 710069, China；²Key Laboratory of Aerospace Medicine of the Ministry of Education, School of Aerospace Medicine, Air Force Medical University, Xi’an 710032, China

Abstract

The aim of the present study was to investigate the effects of short-term ketogenic diet on the low temperature tolerance of mice and the involvement of peroxisome proliferator-activated receptor α (PPARα). C57BL/6J mice were divided into two groups: normal diet (WT+ND) group and ketogenic diet (WT+KD) group. After being fed with normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The changes in core temperature, blood glucose, blood pressure of mice under low temperature condition were detected, and the protein expression levels of PPARα and mitochondrial uncoupling protein 1 (UCP1) were detected by Western blot. PPARα knockout mice were divided into normal diet (PPARα−/−+ND) group and ketogenic diet (PPARα−/−+KD) group. After being fed with the normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The above indicators were also detected. The results showed that, at room temperature, the protein expression levels of PPARα and UCP1 in liver and brown adipose tissue of WT+KD group were significantly up-regulated, compared with those of WT+ND group. Under low temperature condition, compared with WT+ND, the core temperature and blood glucose of WT+KD group were increased, while mean arterial pressure was decreased; The ketogenic diet up-regulated PPARα protein expression in brown adipose tissue, as well as UCP1 protein expression in liver and brown adipose tissue of WT+KD group. Under low temperature condition, compared to WT+ND group, PPARα−/−+ND group exhibited decreased core temperature and down-regulated PPARα and UCP1 protein expression levels in liver, skeletal muscle, white and brown adipose tissue. Compared to the PPARα−/−+ND group, the PPARα−/−+KD group exhibited decreased core temperature and did not show any difference in the protein expression of UCP1 in liver, skeletal muscle, white and brown adipose tissue. These results suggest that the ketogenic diet promotes UCP1 expression by up-regulating PPARα, thus improving low temperature tolerance of mice. Therefore, short-term ketogenic diet can be used as a potential intervention to improve the low temperature tolerance.

Key words: ketogenic diet; low temperature tolerance; peroxisome proliferator-activated receptor α

收稿日期：　　录用日期：

通讯作者：张星　　E-mail: zhangxing@fmmu.edu.cn

DOI: 10.13294/j.aps.2023.0028

引用本文：

李宸涵, 张伟, 王盼盼, 张鹏飞, 安冏, 杨红燕, 高峰, 武桂铃, 张星. 生酮饮食通过上调肝脏和棕色脂肪组织PPARα提高小鼠耐低温能力[J]. 生理学报 2023; 75 (2): 171-178.

LI Chen-Han, ZHANG Wei, WANG Pan-Pan, ZHANG Peng-Fei, AN Jiong, YANG Hong-Yan, GAO Feng, WU Gui-Ling, ZHANG Xing. Ketogenic diet improves low temperature tolerance in mice by up-regulating PPARα in the liver and brown adipose tissue. Acta Physiol Sin 2023; 75 (2): 171-178 (in Chinese with English abstract).