High doses of butyrate induce a reversible body temperature drop through transient proton leak in mitochondria of brain neurons

doi:10.1016/j.lfs.2021.119614

	High doses of butyrate induce a reversible body temperature drop through transient proton leak in mitochondria of brain neurons
	Xu, Yanhong 1,2,3; Peng, Shiqiao 1,2; Cao, Xinyu 1,2; Qian, Shengnan 2; Shen, Shuang 2; Luo, Juntao 2; Zhang, Xiaoying 2; Sun, Hongbin4 ; Shen, Wei L.4; Jia, Weiping 1; Ye, Jianping 1,2
	2021-08-01
发表期刊	LIFE SCIENCES (IF:5.2[JCR-2023],5.3[5-Year])
ISSN	0024-3205
EISSN	1879-0631
卷号	278
DOI	10.1016/j.lfs.2021.119614
摘要	Aims: Sodium butyrate (SB) is a major product of gut microbiota with signaling activity in the human body. It has become a dietary supplement in the treatment of intestinal disorders. However, the toxic effect of overdosed SB and treatment strategy remain unknown. The two issues are addressed in current study. Materials and methods: SB (0.3 & ndash;2.5 g/kg) was administrated through a single peritoneal injection in mice. The core body temperature and mitochondrial function in the brown adipose tissue and brain were monitored. Pharmacodynamics, targeted metabolomics, electron microscope, oxygen consumption rate and gene knockdown were employed to dissect the mechanism for the toxic effect. Key findings: The temperature was reduced by SB (1.2 & ndash;2.5 g/kg) in a dose-dependent manner in mice for 2 & ndash;4 h. In the brain, the effect was associated with SB elevation and neurotransmitter reduction. Metabolites changes were seen in the glycolysis, TCA cycle and pentose phosphate pathways. Adenine nucleotide translocase (ANT) was activated by butyrate for proton transportation leading to a transient potential collapse through proton leak. The SB activity was attenuated by ANT inhibition from gene knockdown or pharmacological blocker. ROS was elevated by SB for the increased ANT activity in proton leak in Neuro-2a. Significance: Excessive SB generated an immediate and reversible toxic effect for inhibition of body temperature through transient mitochondrial dysfunction in the brain. The mechanism was quick activation of ANT proteins for potential collapse in mitochondria. ROS may be a factor in the ANT activation by SB.
关键词	Sodium butyrate Mitochondria MPTP Energy metabolism ANT
收录类别	SCIE
语种	英语
WOS研究方向	Research & Experimental Medicine ; Pharmacology & Pharmacy
WOS类目	Medicine, Research & Experimental ; Pharmacology & Pharmacy
WOS记录号	WOS:000663323800005
出版者	PERGAMON-ELSEVIER SCIENCE LTD
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/127559
专题	生命科学与技术学院_PI研究组_沈伟组
通讯作者	Ye, Jianping
作者单位	1.Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, Shanghai Diabet Inst, Shanghai 200233, Peoples R China; 2.Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, Cent Lab, Shanghai 200233, Peoples R China; 3.Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, Neurol Dept, Shanghai 200233, Peoples R China; 4.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
推荐引用方式 GB/T 7714	Xu, Yanhong,Peng, Shiqiao,Cao, Xinyu,et al. High doses of butyrate induce a reversible body temperature drop through transient proton leak in mitochondria of brain neurons[J]. LIFE SCIENCES,2021,278.
APA	Xu, Yanhong.,Peng, Shiqiao.,Cao, Xinyu.,Qian, Shengnan.,Shen, Shuang.,...&Ye, Jianping.(2021).High doses of butyrate induce a reversible body temperature drop through transient proton leak in mitochondria of brain neurons.LIFE SCIENCES,278.
MLA	Xu, Yanhong,et al."High doses of butyrate induce a reversible body temperature drop through transient proton leak in mitochondria of brain neurons".LIFE SCIENCES 278(2021).