Life metabolism最新文献_第8页

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 eCollection Date: 2022-12-01 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":"10.1093/lifemeta/loac028","url":null,"abstract":"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 determine the 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 the 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 m6A 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":"488 4","pages":"270-284"},"PeriodicalIF":0.0,"publicationDate":"2022-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41274212","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

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 eCollection Date: 2022-12-01 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, Ping Gao, Canjun Zhu, Qingyan Jiang, Gang 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, Ping Gao, Canjun Zhu, Qingyan Jiang, Gang Shu","doi":"10.1093/lifemeta/loac026","DOIUrl":"10.1093/lifemeta/loac026","url":null,"abstract":"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 knockout 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 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":" ","pages":"285-297"},"PeriodicalIF":0.0,"publicationDate":"2022-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49349853","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

Coldness impedes tumor growth. 寒冷阻碍肿瘤生长

Life metabolism Pub Date : 2022-09-15 eCollection Date: 2022-12-01 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 eCollection Date: 2022-10-01 DOI: 10.1093/lifemeta/loac021

Jinglin Zhu, Sin Man Lam, Leilei Yang, Jingjing Liang, Mei Ding, Guanghou Shui, Xun Huang

{"title":"Reduced phosphatidylcholine synthesis suppresses the embryonic lethality of seipin deficiency.","authors":"Jinglin Zhu, Sin Man Lam, Leilei Yang, Jingjing Liang, Mei Ding, Guanghou Shui, Xun Huang","doi":"10.1093/lifemeta/loac021","DOIUrl":"10.1093/lifemeta/loac021","url":null,"abstract":"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 Caenorhabditis 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. In addition, the suppression is enhanced by the knockdown of phospholipid scramblase epg-3. Therefore, seipin and PC 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":" ","pages":"175-189"},"PeriodicalIF":0.0,"publicationDate":"2022-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45950703","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

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 eCollection Date: 2022-10-01 DOI: 10.1093/lifemeta/loac020

Xiu-Fang Xin, Jian-Min Zhou

引用次数: 0

Functional diversity and metabolic engineering of plant-specialized metabolites. 植物特化代谢物的功能多样性与代谢工程

Life metabolism Pub Date : 2022-08-25 eCollection Date: 2022-10-01 DOI: 10.1093/lifemeta/loac019

Shaoqun Zhou, Yongshuo Ma, Yi Shang, Xiaoquan Qi, Sanwen Huang, Jiayang Li

{"title":"Functional diversity and metabolic engineering of plant-specialized metabolites.","authors":"Shaoqun Zhou, Yongshuo Ma, Yi Shang, Xiaoquan Qi, Sanwen Huang, Jiayang Li","doi":"10.1093/lifemeta/loac019","DOIUrl":"10.1093/lifemeta/loac019","url":null,"abstract":"Plants are talented biochemists that produce a broad diversity of small molecules. These so-called specialized metabolites (SMs) play critical roles in the adaptive evolution of plants to defend against biotic and abiotic stresses, attract pollinators, and modulate soil microbiota for their own benefits. Many plant SMs have been used as nutrition and flavor compounds in our daily food, as well as drugs for treatment of human diseases. Current multi-omics tools have significantly accelerated the process of biosynthetic pathway elucidation in plants through correlation analyses, genetic mapping, and de novo biosynthetic gene cluster predictions. Understanding the biosynthesis of plant SMs has enabled reconstitution of naturally occurring specialized metabolic pathways in microbial hosts, providing a sustainable supply of these high-value molecules. In this review, we illustrate the general functions of several typical plant SMs in natural ecosystems and for human societies. We then provide an overview of current methods elucidating the biosynthetic pathways of plant SMs, and synthetic biology strategies that optimize the efficiency of heterologous biosynthetic pathways in microbial hosts. Moving forward, dissection of the functions and application of plant SMs by using current multidiscipline approaches would be greatly benefit to the scientific community and human societies.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":" ","pages":"109-121"},"PeriodicalIF":0.0,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47444542","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

α-Ketoglutaric acid: a new chance for male fertility preservation. α-酮戊二酸：保存男性生育能力的新机会

Life metabolism Pub Date : 2022-08-23 eCollection Date: 2022-08-01 DOI: 10.1093/lifemeta/loac015

Fucheng Dong, Wei Li

引用次数: 0

Ketone bodies determine the female reproductive lifespan. 酮体通过调节卵巢储备来决定女性的生殖寿命

Life metabolism Pub Date : 2022-08-18 eCollection Date: 2022-10-01 DOI: 10.1093/lifemeta/loac018

Long Yan, Hongmei Wang

引用次数: 0

The neonatal ketone body is important for primordial follicle pool formation and regulates ovarian ageing in mice. 新生酮体在小鼠原始卵泡池形成和调节卵巢老化中起重要作用

Life metabolism Pub Date : 2022-08-11 eCollection Date: 2022-10-01 DOI: 10.1093/lifemeta/loac017

Xin-Ying Wang, Xin-Ge Zhang, Yong-Juan Sang, Dan-Yang Chong, Xiao-Qiang Sheng, Hai-Quan Wang, Chao-Fan Yang, GuiJun Yan, Hai-Xiang Sun, Chao-Jun Li

{"title":"The neonatal ketone body is important for primordial follicle pool formation and regulates ovarian ageing in mice.","authors":"Xin-Ying Wang, Xin-Ge Zhang, Yong-Juan Sang, Dan-Yang Chong, Xiao-Qiang Sheng, Hai-Quan Wang, Chao-Fan Yang, GuiJun Yan, Hai-Xiang Sun, Chao-Jun Li","doi":"10.1093/lifemeta/loac017","DOIUrl":"10.1093/lifemeta/loac017","url":null,"abstract":"Adverse nutritional conditions during the perinatal stage are related to early menopause in adulthood; however, the underlying mechanism is still unclear. Herein, we revealed that colostrum-activated ketone body elevation during the postnatal stage regulated primordial follicle reservoir size and then affected ovarian ageing. We found that the expression of the ketogenesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2 (Hmgcs2) was largely enhanced during primordial follicle pool formation after birth and might be activated in the ovaries by colostrum. Reactive oxygen species (ROS) elevation in the ovaries leads to follicle apoptosis to deplete damaged follicles, while Hmgcs2 deficiency enhances follicle apoptosis and thus decreases the size of the primordial follicle pool and leads to premature ovarian ageing (POA), which might be related to the activation of cellular endogenous antioxidant system. All these defects could be rescued by ketone body administration, which suppressed ROS-activated follicle apoptosis. Our results suggest that the internal metabolic homeostasis of newborn mice is critical for the primordial reservoir and that any intrauterine and perinatal undernutrition could result in POA.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":" ","pages":"149-160"},"PeriodicalIF":0.0,"publicationDate":"2022-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44521752","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 Ca²⁺ cycling defect connects insulin resistance and heart failure. Ca2+循环缺陷与胰岛素抵抗和心力衰竭有关。

Life metabolism Pub Date : 2022-08-01 Epub Date: 2022-08-04 DOI: 10.1093/lifemeta/loac014

Qian Shi, Duane D Hall, Long-Sheng Song

引用次数: 0