Life metabolism最新文献_第9页

Safety and immunogenicity of a modified COVID-19 mRNA vaccine, SYS6006, as a fourth-dose booster following three doses of inactivated vaccines in healthy adults: an open-labeled Phase 1 trial. 一种改良的COVID-19 mRNA疫苗SYS6006在健康成人中作为三剂灭活疫苗后的第四剂加强剂的安全性和免疫原性:一项开放标记的1期试验

Life metabolism Pub Date : 2023-05-10 eCollection Date: 2023-06-01 DOI: 10.1093/lifemeta/load019

Yuzhou Gui, Ye Cao, Jiajin He, Chunyang Zhao, Wei Zheng, Ling Qian, Jie Cheng, Chengyin Yu, Chen Yu, Kun Lou, Gangyi Liu, Jingying Jia

{"title":"Safety and immunogenicity of a modified COVID-19 mRNA vaccine, SYS6006, as a fourth-dose booster following three doses of inactivated vaccines in healthy adults: an open-labeled Phase 1 trial.","authors":"Yuzhou Gui, Ye Cao, Jiajin He, Chunyang Zhao, Wei Zheng, Ling Qian, Jie Cheng, Chengyin Yu, Chen Yu, Kun Lou, Gangyi Liu, Jingying Jia","doi":"10.1093/lifemeta/load019","DOIUrl":"10.1093/lifemeta/load019","url":null,"abstract":"The continuous emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants led to a rapid decline in protection efficacy and neutralizing titers even after three doses of COVID-19 vaccines. Here, we report an open-labeled Phase I clinical trial of a modified mRNA vaccine (SYS6006) as a fourth-dose booster in healthy adults. Eighteen eligible participants, who had completed three doses of inactivated COVID-19 vaccines, received a fourth boosting dose of SYS6006-20 μg. Eighteen convalescent COVID-19 patients were enrolled for the collection of serum samples as a comparator of immunogenicity. The primary endpoint of this trial was titers of anti-receptor binding domain of spike glycoprotein (RBD) antibodies of the Omicron strain (BA.2 and BA.4/5) in serum; titers of neutralizing antibodies against pseudovirus of the Omicron strain (BA.2 and BA.4/5). The secondary endpoint was the incidence of adverse events within 30 days after the boosting. The exploratory endpoint was the cellular immune responses (interferon gamma, IFN-γ). This trial was registered with the Chinese Clinical Trial Registry website. No serious adverse events were reported within 30 days after vaccination. No Grade 3 fever or serious adverse event was reported in the SYS6006 group. Notably, SYS6006 elicited higher titers and longer increases in anti-RBD antibodies and neutralizing antibodies (>90 days) compared with the convalescent group (P < 0.0001) against Omicron strain (BA.2 and BA.4/5). Besides, higher positive spots of T-cell-secreting IFN-γ were observed in the SYS6006 group than those in the convalescent group (P < 0.05). These data demonstrated that SYS6006 was well tolerated and highly immunogenic, generating a stronger and more durable immune response against different variants of SARS-CoV-2.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":" ","pages":"load019"},"PeriodicalIF":0.0,"publicationDate":"2023-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45992088","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

Opioid growth factor receptor promotes adipose tissue thermogenesis via enhancing lipid oxidation. 阿片生长因子受体通过增强脂质氧化促进脂肪组织产热

Life metabolism Pub Date : 2023-05-04 eCollection Date: 2023-06-01 DOI: 10.1093/lifemeta/load018

Shan Zhang, Jianhui Chen, Qingqing Li, Wenwen Zeng

{"title":"Opioid growth factor receptor promotes adipose tissue thermogenesis via enhancing lipid oxidation.","authors":"Shan Zhang, Jianhui Chen, Qingqing Li, Wenwen Zeng","doi":"10.1093/lifemeta/load018","DOIUrl":"10.1093/lifemeta/load018","url":null,"abstract":"The thermogenic brown and beige adipocytes consume fatty acids and generate heat to maintain core body temperature in the face of cold challenges. Since their validated presence in humans, the activation of thermogenic fat has been an attractive target for treating obesity and related metabolic diseases. Here, we reported that the opioid growth factor receptor (Ogfr) was highly expressed in adipocytes and promoted thermogenesis. The mice with genetic deletion of Ogfr in adipocytes displayed an impaired capacity to counter environmental cold challenges. Meanwhile, Ogfr ablation in adipocytes led to reduced fatty acid oxidation, enhanced lipid accumulation, impaired glucose tolerance, and exacerbated tissue inflammation under chronic high-fat diet (HFD)-fed conditions. At the cellular level, OGFr enhanced the production of mitochondrial trifunctional protein subunit α (MTPα) and also interacted with MTPα, thus promoting fatty acid oxidation. Together, our study demonstrated the important role of OGFr in fatty acid metabolism and adipose thermogenesis.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":" ","pages":"load018"},"PeriodicalIF":0.0,"publicationDate":"2023-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45596018","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

Lactate: an intracellular metabolite regulates cell cycle progression. 乳酸：一种细胞内代谢产物调节细胞周期进程

Life metabolism Pub Date : 2023-04-24 eCollection Date: 2023-08-01 DOI: 10.1093/lifemeta/load017

Jinke Cheng, Edward T H Yeh

引用次数: 0

Three 700$ awards available from Life Metabolism to support conference attendance. Life Metabolism提供三个700美元的奖励，以支持会议出席

Life metabolism Pub Date : 2023-04-19 eCollection Date: 2023-06-01 DOI: 10.1093/lifemeta/load016

John R Speakman

引用次数: 0

Weight loss increases skeletal muscle mitochondrial energy efficiency in obese mice. 减肥可提高肥胖小鼠骨骼肌线粒体的能量效率。

Life metabolism Pub Date : 2023-04-01 Epub Date: 2023-04-04 DOI: 10.1093/lifemeta/load014

Patrick J Ferrara, Marisa J Lang, Jordan M Johnson, Shinya Watanabe, Kelsey L McLaughlin, J Alan Maschek, Anthony R P Verkerke, Piyarat Siripoksup, Amandine Chaix, James E Cox, Kelsey H Fisher-Wellman, Katsuhiko Funai

{"title":"Weight loss increases skeletal muscle mitochondrial energy efficiency in obese mice.","authors":"Patrick J Ferrara, Marisa J Lang, Jordan M Johnson, Shinya Watanabe, Kelsey L McLaughlin, J Alan Maschek, Anthony R P Verkerke, Piyarat Siripoksup, Amandine Chaix, James E Cox, Kelsey H Fisher-Wellman, Katsuhiko Funai","doi":"10.1093/lifemeta/load014","DOIUrl":"10.1093/lifemeta/load014","url":null,"abstract":"Weight loss from an overweight state is associated with a disproportionate decrease in whole-body energy expenditure that may contribute to the heightened risk for weight regain. Evidence suggests that this energetic mismatch originates from lean tissue. Although this phenomenon is well documented, the mechanisms have remained elusive. We hypothesized that increased mitochondrial energy efficiency in skeletal muscle is associated with reduced expenditure under weight loss. Wildtype (WT) male C57BL6/N mice were fed with high fat diet for 10 weeks, followed by a subset of mice that were maintained on the obesogenic diet (OB) or switched to standard chow to promote weight loss (WL) for additional 6 weeks. Mitochondrial energy efficiency was evaluated using high-resolution respirometry and fluorometry. Mass spectrometric analyses were employed to describe the mitochondrial proteome and lipidome. Weight loss promoted ~50% increase in the efficiency of oxidative phosphorylation (ATP produced per O2 consumed, or P/O) in skeletal muscle. However, weight loss did not appear to induce significant changes in mitochondrial proteome, nor any changes in respiratory supercomplex formation. Instead, it accelerated the remodeling of mitochondrial cardiolipin (CL) acyl-chains to increase tetralinoleoyl CL (TLCL) content, a species of lipids thought to be functionally critical for the respiratory enzymes. We further show that lowering TLCL by deleting the CL transacylase tafazzin was sufficient to reduce skeletal muscle P/O and protect mice from diet-induced weight gain. These findings implicate skeletal muscle mitochondrial efficiency as a novel mechanism by which weight loss reduces energy expenditure in obesity.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"2 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10195096/pdf/nihms-1890467.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9770381","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

Glutathione restoration: a sword to combat skeletal muscle stem cell aging. 谷胱甘肽修复：对抗骨骼肌干细胞衰老的利剑

Life metabolism Pub Date : 2023-03-31 eCollection Date: 2023-06-01 DOI: 10.1093/lifemeta/load012

Zeming Wu, Jie Ren, Guang-Hui Liu

引用次数: 0

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