Life metabolism最新文献_第9页

CLN3 clinches lysosomes in clearance of glycerophospholipids CLN3结合溶酶体清除甘油磷脂

Life metabolism Pub Date : 2022-10-19 DOI: 10.1093/lifemeta/loac029

Guang Lu, Han-Ming Shen

引用次数: 0

WTAP Regulates Postnatal Development of Brown Adipose Tissue by stabilizing METTL3 in mice WTAP通过稳定METTL3调节小鼠出生后棕色脂肪组织的发育

Life metabolism Pub Date : 2022-10-10 DOI: 10.1093/lifemeta/loac028

Yuqin Wang, Xinzhi Li, Cenxi Liu, Liying Zhou, Lei Shi, Zhiguo Zhang, Long Chen, Ming Gao, Lanyue Gao, Yuanyuan Xu, He Huang, Jin Li, Zheng Chen

{"title":"WTAP Regulates Postnatal Development of Brown Adipose Tissue by stabilizing METTL3 in mice","authors":"Yuqin Wang, Xinzhi Li, Cenxi Liu, Liying Zhou, Lei Shi, Zhiguo Zhang, Long Chen, Ming Gao, Lanyue Gao, Yuanyuan Xu, He Huang, Jin Li, Zheng Chen","doi":"10.1093/lifemeta/loac028","DOIUrl":"https://doi.org/10.1093/lifemeta/loac028","url":null,"abstract":"\u0000 Brown adipocyte maturation during postnatal development is essential for brown adipose tissue (BAT) to protect animals against cold. Impaired maturation of brown adipocytes leads to cold intolerance. However, the molecular mechanisms that determines maturation of brown adipocytes during postnatal development are not fully understood. Here we identify Wilms’ tumor 1-associating protein (WTAP) as an essential regulator in the postnatal development and maturation of BAT. BAT-specific knockout of Wtap (Wtap-BKO) severely impairs maturation of BAT in vivo by decreasing the expression of BAT-selective genes, leading to whitening of interscapular BAT (iBAT). Single nucleus RNA-sequencing analysis shows the dynamic changes of cell heterogeneity in iBAT of Wtap-BKO mice. Adult mice with WTAP deficiency in BAT display hypothermic and succumb to acute cold challenge. Mechanistically, WTAP deficiency decreases m 6A mRNA modification by reducing the protein stability of METTL3. BAT-specific overexpression of Mettl3 partially rescues the phenotypes observed in Wtap-BKO mice. These data demonstrate that WTAP/METTL3 plays an essential role in iBAT postnatal development and thermogenesis.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41274212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Inhibiting lysosomal aldolase: a magic bullet for AMPK activation in treating metabolic disease? 抑制溶酶体醛缩酶：AMPK激活治疗代谢性疾病的灵丹妙药？

Life metabolism Pub Date : 2022-10-10 DOI: 10.1093/lifemeta/loac027

D. Carling

引用次数: 0

Sirtuins are Not Conserved Longevity Genes. Sirtuins不是保守的长寿基因。

Life metabolism Pub Date : 2022-10-01 DOI: 10.1093/lifemeta/loac025

Charles Brenner

{"title":"Sirtuins are Not Conserved Longevity Genes.","authors":"Charles Brenner","doi":"10.1093/lifemeta/loac025","DOIUrl":"https://doi.org/10.1093/lifemeta/loac025","url":null,"abstract":"It is central to biology that sequence conservation suggests functional conservation. Animal longevity is an emergent property of selected traits that integrates capacities to perform physical and mental functions after reproductive maturity. Though the yeast SIR2 gene was nominated as a longevity gene based on extended replicative longevity of old mother cells, this is not a selected trait: SIR2 is selected against in chronological aging and the direct targets of SIR2 in replicative lifespan are not conserved. Though it would be difficult to imagine how a gene that advantages 1 in 5 million yeast cells could have anticipated causes of aging in animals, overexpression of SIR2 homologs was tested in invertebrates for longevity. Because artifactual positive results were reported years before they were sorted out and because it was not known that SIR2 functions as a pro-aging gene in yeast chronological aging and in flies subject to amino acid deprivation, a global pursuit of longevity phenotypes was driven by a mixture of framing bias, confirmation bias and hype. Review articles that propagate these biases are so rampant that few investigators have considered how weak the case ever was for sirtuins as longevity genes. Acknowledging that a few positive associations between sirtuins and longevity have been identified after thousands of person-years and billions of dollars of effort, we review the data and suggest rejection of the notions that sirtuins 1) have any specific connection to lifespan in animals and 2) are primary mediators of the beneficial effects of NAD repletion.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9637428","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: 6

AKG/OXGR1 promotes skeletal muscle blood flow and metabolism by relaxing vascular smooth muscle AKG/OXGR1通过放松血管平滑肌促进骨骼肌血液流动和代谢

Life metabolism Pub Date : 2022-09-29 DOI: 10.1093/lifemeta/loac026

Jinping Yang, Guli Xu, Yiming Xu, Pei Luo, Yexian Yuan, Lin Yao, Jingjing Zhou, Yunlong Zhu, Ishwari Gyawali, Chang Xu, Jinlong Feng, Zewei Ma, Yuxian Zeng, Songbo Wang, P. Gao, Canjun Zhu, Q. Jiang, G. Shu

{"title":"AKG/OXGR1 promotes skeletal muscle blood flow and metabolism by relaxing vascular smooth muscle","authors":"Jinping Yang, Guli Xu, Yiming Xu, Pei Luo, Yexian Yuan, Lin Yao, Jingjing Zhou, Yunlong Zhu, Ishwari Gyawali, Chang Xu, Jinlong Feng, Zewei Ma, Yuxian Zeng, Songbo Wang, P. Gao, Canjun Zhu, Q. Jiang, G. Shu","doi":"10.1093/lifemeta/loac026","DOIUrl":"https://doi.org/10.1093/lifemeta/loac026","url":null,"abstract":"\u0000 In response to contraction during exercise, skeletal muscle growth and metabolism are dynamically regulated by nerve action, blood flow and metabolic feedback. α-ketoglutarate (AKG), a bioactive intermediate in the tricarboxylic acid cycle released during exercise, has been shown to promote skeletal muscle hypertrophy. However, the underlying mechanism of AKG in regulating skeletal muscle development and metabolism is still less known. 2-Oxoglutarate receptor 1 (OXGR1), the endogenous AKG receptor, is found to be distributed in the vascular smooth muscle (VSM) of skeletal muscles. OXGR1 knockout results in skeletal muscle atrophy, accompanied by decreased expression of myosin heavy chain I (MyHC I), capillary density, and endurance exercise capacity. Furthermore, the study found that dietary AKG supplementation increased mice endurance exercise distance, MyHC I/MyHC IIb ratio, arteriole and capillary densities in skeletal muscle. Meanwhile, acute AKG administration gradually increased the blood flow in the lower limbs. Further, by using OXGR1 global knock-out and OXGR1 VSM specific (MYH11-Cre × OXGR1-FloxP) knockdown models, we found that OXGR1 in VSM is essential for AKG-induced improvement of skeletal muscle performances. According to the in vitro study, AKG expanded the cell area in VSM with a decreased intracellular pH (pHi) by OXGR1. Our results demonstrated a novel role of AKG/OXGR1 in VSM of skeletal muscle to regulate blood flow and then enhance slow muscle fiber conversion and capillarization. These findings provide a theoretical basis for the AKG/OXGR1 signaling pathway to maintain human muscle function and improve meat production and livestock and poultry meat quality.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49349853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reprograming yeast for anticancer vinblastine synthesis 重组酵母合成抗癌长春花碱

Life metabolism Pub Date : 2022-09-22 DOI: 10.1093/lifemeta/loac024

Tian Ma, Zixin Deng

引用次数: 0

Less is more: seipin, phospholipids, and embryogenesis 少即是多:磷脂，磷脂和胚胎发生

Life metabolism Pub Date : 2022-09-17 DOI: 10.1093/lifemeta/loac023

Bin Liang, J. Watts

引用次数: 1

Coldness impedes tumor growth 寒冷阻碍肿瘤生长

Life metabolism Pub Date : 2022-09-15 DOI: 10.1093/lifemeta/loac022

Shudi Luo, Xiaoming Jiang, Zhimin Lu

引用次数: 0

Reduced phosphatidylcholine synthesis suppresses the embryonic lethality of seipin deficiency 磷脂酰胆碱合成减少可抑制赛品缺乏症的胚胎致死率

Life metabolism Pub Date : 2022-09-08 DOI: 10.1093/lifemeta/loac021

Jinglin Zhu, S. Lam, Lei-lei Yang, Jingjing Liang, Mei Ding, G. Shui, Xun Huang

{"title":"Reduced phosphatidylcholine synthesis suppresses the embryonic lethality of seipin deficiency","authors":"Jinglin Zhu, S. Lam, Lei-lei Yang, Jingjing Liang, Mei Ding, G. Shui, Xun Huang","doi":"10.1093/lifemeta/loac021","DOIUrl":"https://doi.org/10.1093/lifemeta/loac021","url":null,"abstract":"\u0000 Seipin plays a vital role in lipid droplet homeostasis and its deficiency causes congenital generalized lipodystrophy type II in humans. It is not known whether the physiological defects are all caused by cellular lipid droplet defects. Loss-of-function mutation of seip-1, the C. elegans seipin ortholog, causes embryonic lethality and lipid droplet abnormality. We uncover nhr-114 and spin-4 as two suppressors of seip-1 embryonic lethality. Mechanistically, nhr-114 and spin-4 act in the “B12-one-carbon cycle-phosphatidylcholine (PC)” axis and reducing PC synthesis suppresses the embryonic lethality of seip-1 mutants. Conversely, PC deficiency enhances the lipid droplet abnormality of seip-1 mutants. The suppression of seip-1 embryonic lethality by PC reduction requires polyunsaturated fatty acid (PUFA). In addition, the suppression is enhanced by knockdown of phospholipid scramblase epg-3. Therefore, seipin and phosphatidylcholine exhibit opposite actions in embryogenesis, while they function similarly in lipid droplet homeostasis. Our results demonstrate that seipin-mediated embryogenesis is independent of lipid droplet homeostasis.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45950703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Impaired condensate formation is to blame for failed disease resistance in plants 凝结水形成受损是植物抗病性失败的原因

Life metabolism Pub Date : 2022-09-01 DOI: 10.1093/lifemeta/loac020

Xiu-Fang Xin, Jian-Min Zhou

引用次数: 0