Effects of Fibroblast Growth Factor 21 on Lactate Uptake and Usage in Mice with Diabetes-Associated Cognitive Decline

doi:10.1007/s12035-022-02926-z

科研成果详情

题名	Effects of Fibroblast Growth Factor 21 on Lactate Uptake and Usage in Mice with Diabetes-Associated Cognitive Decline
作者	Zhao, Liangcai1; Jiang, Haowei 1; Xie, Jiaojiao1; Shen, Danjie1; Yi, Qingqing1; Yan, Jiapin1; Li, Chen 1; Zheng, Hong1; Gao, Hongchang1,2
发表日期	2022-09
发表期刊	MOLECULAR NEUROBIOLOGY 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	Diabetes mellitus Fibroblast growth factor 21 Monocarboxylate transporter Lactate Learning and memory
其他关键词	NEURONAL MONOCARBOXYLATE TRANSPORTER ; MITOCHONDRIAL-FUNCTION ; METABOLIC ALTERATIONS ; BRAIN ; EXPRESSION ; FGF21 ; ASTROCYTES ; MCT2 ; INSULIN ; SYSTEM
摘要	Fibroblast growth factor 21 (FGF21) is an endocrine hormone that exerts beneficial effects on glucose and lipid metabolic homeostasis. However, the impact of FGF21 on type 1 diabetes-associated cognitive decline (DACD) and its mechanisms of action remain unclear. In this study, we aimed to evaluate the effects of FGF21 on lactate uptake and usage in a mouse model of streptozotocin-induced DACD. Six-week-old male C57BL/6 mice were divided into the control, diabetic, and FGF21 (which received 2 mg/kg recombinant human FGF21) groups. At the end of the treatment period, learning and memory performance, nuclear magnetic resonance-based metabonomics, and expressions of various hippocampal protein were analyzed to determine the efficacy of FGF21. The results showed that compared to the control mice, the diabetic mice had reduced long-term memory performance after the hyperglycemic insult; decreased hippocampal levels of lactate dehydrogenase-B (LDH-B) activity, bioenergy metabolites, and monocarboxylate transporter 2 (MCT2); and increased lactate levels. Impaired phosphoinositide 3-kinase (PI3K) signaling was also observed in the diabetic mice. However, FGF21 treatment improved LDH-B activity, beta-nicotinamide adenine dinucleotide, and ATP levels, and increased MCT2 expression and PI3K signaling pathway, which in turn improved the learning and memory defects. These findings demonstrated that the effects of FGF21 on DACD were associated with its ability to improve LDH-B-mediated lactate usage and MCT2-dependent lactate uptake. Further, these beneficial effects of FGF21 in the hippocampus were mediated by the PI3K signaling pathways.
资助项目	Natural Science Foundation of Zhejiang Province [LY22H070003]; National Natural Science Foundation of China [81770830, 21974096, 81771386]
出版者	SPRINGER
出版地	NEW YORK
ISSN	0893-7648
EISSN	1559-1182
卷号	59 期号:9 页码:5656-5672
DOI	10.1007/s12035-022-02926-z
页数	17
WOS类目	Neurosciences
WOS研究方向	Neurosciences & Neurology
WOS记录号	WOS:000816998400001
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	35761156
SCOPUSEID	2-s2.0-85132936025
通讯作者地址	[Zhao, Liangcai]School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China ; [Gao, Hongchang]School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China
Scopus学科分类	Neuroscience (miscellaneous);Neurology;Cellular and Molecular Neuroscience
引用统计	被引频次[WOS]：0 [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/148317
专题	药学院（分析测试中心）卓越中心_老年研究院
通讯作者	Zhao, Liangcai; Gao, Hongchang
作者单位	1.School of Pharmaceutical Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 2.Institute of Aging,Key Laboratory of Alzheimer’s Disease of Zhejiang Province,Wenzhou Medical University,Wenzhou,China
第一作者单位	药学院（分析测试中心）
通讯作者单位	药学院（分析测试中心）
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Zhao, Liangcai,Jiang, Haowei,Xie, Jiaojiao,et al. Effects of Fibroblast Growth Factor 21 on Lactate Uptake and Usage in Mice with Diabetes-Associated Cognitive Decline[J]. MOLECULAR NEUROBIOLOGY,2022,59(9):5656-5672.
APA	Zhao, Liangcai., Jiang, Haowei., Xie, Jiaojiao., Shen, Danjie., Yi, Qingqing., ... & Gao, Hongchang. (2022). Effects of Fibroblast Growth Factor 21 on Lactate Uptake and Usage in Mice with Diabetes-Associated Cognitive Decline. MOLECULAR NEUROBIOLOGY, 59(9), 5656-5672.
MLA	Zhao, Liangcai,et al."Effects of Fibroblast Growth Factor 21 on Lactate Uptake and Usage in Mice with Diabetes-Associated Cognitive Decline".MOLECULAR NEUROBIOLOGY 59.9(2022):5656-5672.