Life metabolism最新文献_第9页

Ablation of Mea6/cTAGE5 in oligodendrocytes significantly impairs white matter structure and lipid content. 少突胶质细胞中Mea6/cTAGE5的消融显著损害白质结构和脂质含量

Life metabolism Pub Date : 2023-03-23 eCollection Date: 2023-04-01 DOI: 10.1093/lifemeta/load010

Tiantian Ma, Wei Mao, Shaohua Zhang, Yaqing Wang, Tao Wang, Jinghua Liu, Lei Shi, Xiang Yu, Rong Xue, Guanghou Shui, Zhiheng Xu

{"title":"Ablation of Mea6/cTAGE5 in oligodendrocytes significantly impairs white matter structure and lipid content.","authors":"Tiantian Ma, Wei Mao, Shaohua Zhang, Yaqing Wang, Tao Wang, Jinghua Liu, Lei Shi, Xiang Yu, Rong Xue, Guanghou Shui, Zhiheng Xu","doi":"10.1093/lifemeta/load010","DOIUrl":"10.1093/lifemeta/load010","url":null,"abstract":"Lipid-rich myelin is a special structure formed by oligodendrocytes wrapping neuronal axons. Abnormal myelin sheath is associated with many neurological diseases. Meningioma-expressed antigen 6 (Mea6)/cutaneous T cell lymphoma-associated antigen 5C (cTAGE5C) plays an important role in vesicle trafficking from the endoplasmic reticulum (ER) to Golgi, and conditional knockout (cKO) of Mea6 in the brain significantly affects neural development and brain function. However, whether the impaired brain function involves the development of oligodendrocytes and white matter beyond neurons remains unclear. In this study, by using different models of diffusion magnetic resonance imaging, we showed that cKO of Mea6 in oligodendrocytes leads to significant impairment of the gross and microstructure of the white matter, as well as a significant decrease of cholesterol and triglycerides in brains. Our lipidomic analysis of purified myelin sheath for the first time showed that Mea6 elimination in oligodendrocytes significantly altered the lipid composition in myelin lipidome, especially the proportion of very long chain fatty acids (VLCFAs). In particular, the levels of most VLCFA-containing phosphatidylcholines were substantially lower in the myelin sheath of the cKO mice. The reduction of VLCFAs is likely due to the downregulated expression of elongation of very long chain fatty acids (ELOVLs). Our study of an animal model with white matter malformation and the comprehensive lipid profiling would provide clues for future studies of the formation of myelin sheath, myelin lipids, and the pathogenesis of white matter diseases.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":" ","pages":"load010"},"PeriodicalIF":0.0,"publicationDate":"2023-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48676341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fluorescent visualization and evaluation of NPC1L1-mediated vesicular endocytosis during intestinal cholesterol absorption in mice. 小鼠肠道胆固醇吸收过程中NPC1L1介导的囊泡内吞作用的荧光可视化和评价

Life metabolism Pub Date : 2023-03-16 eCollection Date: 2023-04-01 DOI: 10.1093/lifemeta/load011

Xiaojing Wu, Xian-Hua Ma, Jie Lin, Xiaohang Yang, Jian-Hui Shi, Zhifang Xie, Yu-Xia Chen, Weiping J Zhang

{"title":"Fluorescent visualization and evaluation of NPC1L1-mediated vesicular endocytosis during intestinal cholesterol absorption in mice.","authors":"Xiaojing Wu, Xian-Hua Ma, Jie Lin, Xiaohang Yang, Jian-Hui Shi, Zhifang Xie, Yu-Xia Chen, Weiping J Zhang","doi":"10.1093/lifemeta/load011","DOIUrl":"10.1093/lifemeta/load011","url":null,"abstract":"Excessive cholesterol absorption from intestinal lumen contributes to the pathogenesis of hypercholesterolemia, which is an independent risk factor for atherosclerotic cardiovascular disease. Niemann-Pick C1-like 1 (NPC1L1) is a major membrane protein responsible for cholesterol absorption, in which the physiological role of vesicular endocytosis is still controversial, and it lacks a feasible tool to visualize and evaluate the endocytosis of NPC1L1 vesicles in vivo. Here, we genetically labeled endogenous NPC1L1 protein with EGFP in a knock-in mouse model, and demonstrated fluorescent visualization and evaluation of the endocytic vesicles of NPC1L1-cago during intestinal cholesterol absorption. The homozygous NPC1L1-EGFP mice have normal NPC1L1 expression pattern as well as cholesterol homeostasis on chow or high-cholesterol diets. The fluorescence of NPC1L1-EGFP fusion protein localizes at the brush border membrane of small intestine, and EGFP-positive vesicles is visualized beneath the membrane as early as 5 min post oral gavage of cholesterol. Of note, the vesicles colocalize with the early endosomal marker early endosome antigen 1 (EEA1) and the filipin-stained free cholesterol. Pretreatment with NPC1L1 inhibitor ezetimibe inhibits the formation of these cholesterol-induced endocytic vesicles. Our data support the notion that NPC1L1-mediated cholesterol absorption is a vesicular endocytic process. NPC1L1-EGFP mice are a useful model for visualizing cellular NPC1L1-cargo vesicle itineraries and for evaluating NPC1L1 activity in vivo in response to diverse pharmacological agents and nutrients.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":" ","pages":"load011"},"PeriodicalIF":0.0,"publicationDate":"2023-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48339678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A metabolic conspiracy drives anti-tumorigenic macrophages. 代谢阴谋驱动抗肿瘤巨噬细胞

Life metabolism Pub Date : 2023-03-11 eCollection Date: 2023-04-01 DOI: 10.1093/lifemeta/load009

Na Li, Tiffany Horng

引用次数: 0

Donut and spheroid mitochondria: eating, regenerating or trash them out? 甜甜圈和球形线粒体:吃掉、再生还是扔掉?

Life metabolism Pub Date : 2023-03-10 eCollection Date: 2023-06-01 DOI: 10.1093/lifemeta/load008

Wen-Xing Ding, Han-Ming Shen

引用次数: 0

Hierarchical inhibition of mTORC1 by glucose starvation-triggered AXIN lysosomal translocation and by AMPK. 葡萄糖饥饿触发的AXIN溶酶体易位和AMPK对mTORC1的分级抑制

Life metabolism Pub Date : 2023-03-01 eCollection Date: 2023-06-01 DOI: 10.1093/lifemeta/load005

Mengqi Li, Xiaoyan Wei, Jinye Xiong, Jin-Wei Feng, Chen-Song Zhang, Sheng-Cai Lin

{"title":"Hierarchical inhibition of mTORC1 by glucose starvation-triggered AXIN lysosomal translocation and by AMPK.","authors":"Mengqi Li, Xiaoyan Wei, Jinye Xiong, Jin-Wei Feng, Chen-Song Zhang, Sheng-Cai Lin","doi":"10.1093/lifemeta/load005","DOIUrl":"10.1093/lifemeta/load005","url":null,"abstract":"When glucose is replete, mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is active and anchored to the lysosomal surface via the two GTPases, Ras-related GTPase (RAG) and Ras homolog enriched in brain (Rheb), which are regulated by Ragulator and tuberous sclerosis complex 2 (TSC2), respectively. When glucose is low, aldolase senses low fructose-1,6-bisphosphate level and promotes the translocation of AXIN-liver kinase B1 (LKB1) to the lysosomal surface, which leads to the activation of AMP-activated protein kinase (AMPK) and the inhibition of RAGs, sundering mTORC1 from the lysosome and causing its inactivation. AMPK can also inactivate mTORC1 by phosphorylating Raptor and TSC2. However, the hierarchy of AXIN- and AMPK-mediated inhibition of mTORC1 remains poorly defined. Here, we show that AXIN translocation does not require AMPK expression or activity. In glucose starvation conditions, knockout of AXIN extended the half-life of mTORC1 inhibition from 15 to 60 min, whereas knockout of AMPK only extended it to 30 min. RAGBGTP (constitutively active RAGB) almost entirely blocked the lysosomal dissociation and inhibition of mTORC1 under glucose starvation, but it did not inhibit AMPK, indicating that under these conditions, it is AXIN lysosomal translocation that inhibits mTORC1, and it does so via inhibition of RAGs. 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), a mimetic of AMP, which activates both cytosolic AMPK and lysosomal AMPK, fully inhibited mTORC1 even when it is stably anchored to the lysosome by RAGBGTP, whereas glucose starvation mildly inhibited such anchored mTORC1. Together, we demonstrate that the lysosomal translocation of AXIN plays a primary role in glucose starvation-triggered inhibition of mTORC1 by inhibiting RAGs, and that AMPK activity inhibits mTORC1 through phosphorylating Raptor and TSC2, especially under severe stress.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"38 2","pages":"load005"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41295836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Type 2 diabetes originated from non-alcoholic fatty liver disease. 2型糖尿病源于非酒精性脂肪肝

Life metabolism Pub Date : 2023-02-21 eCollection Date: 2023-02-01 DOI: 10.1093/lifemeta/load007

Xuelian Xiong, Xiaoying Li

引用次数: 0

You are what you eat: feeding neurons in nutrient regulation of behavior. 你吃什么就是什么:在行为的营养调节中喂养神经元

Life metabolism Pub Date : 2023-02-08 eCollection Date: 2023-02-01 DOI: 10.1093/lifemeta/load006

Jessie C Morrill, Qingchun Tong

引用次数: 0

Leucine deprivation results in antidepressant effects via GCN2 in AgRP neurons. 亮氨酸剥夺通过GCN2在AgRP神经元中产生抗抑郁作用

Life metabolism Pub Date : 2023-02-04 eCollection Date: 2023-02-01 DOI: 10.1093/lifemeta/load004

Feixiang Yuan, Shangming Wu, Ziheng Zhou, Fuxin Jiao, Hanrui Yin, Yuguo Niu, Haizhou Jiang, Shanghai Chen, Feifan Guo

{"title":"Leucine deprivation results in antidepressant effects via GCN2 in AgRP neurons.","authors":"Feixiang Yuan, Shangming Wu, Ziheng Zhou, Fuxin Jiao, Hanrui Yin, Yuguo Niu, Haizhou Jiang, Shanghai Chen, Feifan Guo","doi":"10.1093/lifemeta/load004","DOIUrl":"10.1093/lifemeta/load004","url":null,"abstract":"Essential amino acids (EAAs) are crucial nutrients, whose levels change in rodents and patients with depression. However, how the levels of a single EAA affects depressive behaviors remains elusive. Here, we demonstrate that although deprivation of the EAA leucine has no effect in unstressed mice, it remarkably reverses the depression-like behaviors induced by chronic restraint stress (CRS). This beneficial effect is independent of feeding and is applicable to the dietary deficiency of other EAAs. Furthermore, the effect of leucine deprivation is suppressed by central injection of leucine or mimicked by central injection of leucinol. Moreover, hypothalamic agouti-related peptide (AgRP) neural activity changes during CRS and leucine deprivation, and chemogenetically inhibiting AgRP neurons eliminates the antidepressant effects of leucine deprivation. Finally, the leucine deprivation-regulated behavioral effects are mediated by amino acid sensor general control non-derepressible 2 (GCN2) in AgRP neurons. Taken together, our results suggest a new drug target and/or dietary intervention for the reduction of depressive symptoms.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":" ","pages":"load004"},"PeriodicalIF":0.0,"publicationDate":"2023-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47134845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inter-tissue communication of mitochondrial stress and metabolic health. 线粒体应激与代谢健康的组织间通讯。

Life metabolism Pub Date : 2023-02-01 DOI: 10.1093/lifemeta/load001

Hanlin Zhang, Xinyu Li, Wudi Fan, Sentibel Pandovski, Ye Tian, Andrew Dillin

引用次数: 2

Metabolism along the life journey of T cells. 代谢沿着T细胞的生命之旅。

Life metabolism Pub Date : 2023-02-01 Epub Date: 2023-01-19 DOI: 10.1093/lifemeta/load002

Min Peng, Ming O Li

引用次数: 0