Life metabolism最新文献

{"title":"The deuterated glucose insulin tolerance test: a new tool to delineate insulin-stimulated glucose uptake from suppression of endogenous glucose production.","authors":"Christian A Unger, Marion C Hope, Michael Chase Kettering, Cassidy E Socia, Barton C Rice, Darya S Niamira, William E Cotham, Reilly T Enos","doi":"10.1093/lifemeta/loae036","DOIUrl":"10.1093/lifemeta/loae036","url":null,"abstract":"<p><p>Graphical Abstract.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"4 1","pages":"loae036"},"PeriodicalIF":0.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054460","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}

{"title":"CIDEC/FSP27 exacerbates obesity-related abdominal aortic aneurysm by promoting perivascular adipose tissue inflammation.","authors":"Qing Zhu, Da Luo, Yining Li, Liyang Yu, Zixuan Zhang, Feng Ouyang, Liangkui Li, Manxi Lu, Changyong Hu, Yinuo Dong, Chengxin Ma, Yan Liang, Tong-Jin Zhao, Feng-Jung Chen, Peng Li, Tian-Shu Yang","doi":"10.1093/lifemeta/loae035","DOIUrl":"10.1093/lifemeta/loae035","url":null,"abstract":"<p><p>Abdominal aortic aneurysm (AAA) is strongly correlated with obesity, partially due to the abnormal expansion of abdominal perivascular adipose tissue (PVAT). Cell death-inducing DNA fragmentation factor-like effector C (CIDEC), also known as fat-specific protein 27 (FSP27) in rodents, is specifically expressed in adipose tissue where it mediates lipid droplet fusion and adipose tissue expansion. Whether and how CIDEC/FSP27 plays a role in AAA pathology remains elusive. Here, we show that FSP27 exacerbates obesity and angiotensin Ⅱ (Ang Ⅱ)-induced AAA progression. FSP27 deficiency in mice inhibited high-fat diet-induced PVAT expansion and inflammation. Both global and adipose tissue-specific FSP27 ablation significantly decreased obesity-related AAA incidence. Deficiency of FSP27 in adipocytes abrogated matrix metalloproteinase-12 (MMP12) expression in aortic tissues. Infiltrated macrophages, which partially colocalize with MMP12, were significantly decreased in the FSP27-deficient aorta. Mechanistically, knockdown of <i>Fsp27</i> in 3T3-L1 adipocytes inhibited C-C motif chemokine ligand 2 (CCL2) expression and secretion through a c-Jun N-terminal kinase (JNK)-dependent pathway, thereby leading to reduced induction of macrophage migration, while <i>Cidec</i> overexpression rescued this effect. Overall, our study demonstrates that CIDEC/FSP27 in adipose tissue contributes to obesity-related AAA formation, at least in part, by enhancing PVAT inflammation and macrophage infiltration, thus shedding light on its significance as a key regulator in the context of obesity-related AAA.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"4 1","pages":"loae035"},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054455","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}

{"title":"Soy peptide as an anecdote to undernutrition.","authors":"Mark P Mattson","doi":"10.1093/lifemeta/loae034","DOIUrl":"10.1093/lifemeta/loae034","url":null,"abstract":"","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"3 5","pages":"loae034"},"PeriodicalIF":0.0,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054450","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}

{"title":"Type 2 diabetes: a sacrifice program handling energy surplus.","authors":"Jianping Ye, Jun Yin","doi":"10.1093/lifemeta/loae033","DOIUrl":"10.1093/lifemeta/loae033","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is closely associated with obesity, while interactions between the two diseases remain to be fully elucidated. To this point, we offer this perspective to introduce a set of new insights into the interpretation of T2DM spanning the etiology, pathogenesis, and treatment approaches. These include a definition of T2DM as an energy surplus-induced diabetes characterized by the gradual decline of β cell insulin secretion function, which ultimately aims to prevent the onset of severe obesity through mechanisms of weight loss. The body employs three adaptive strategies in response to energy surplus: the first one is adipose tissue expansion to store the energy for weight gain under normal weight conditions; the second one is insulin resistance to slow down adipose tissue expansion and weight gain under overweight conditions; and the third one is the onset of T2DM following β cell failure to reverse the weight gain in obese conditions. The primary signaling molecules driving the compensatory responses are adenosine derivatives, such as adenosine triphosphate (ATP), acetyl coenzyme A (acetyl-CoA), and reduced nicotinamide adenine dinucleotide (NADH). These molecules exert their effects through allosteric, post-translational, and transcriptional regulation of metabolic pathways. The insights suggest that insulin resistance and T2DM are protective mechanisms in the defense against excessive adiposity to avert severe obesity. The perspective provides a unified framework explaining the interactions between the two diseases and opens new avenues in the study of T2DM.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"3 6","pages":"loae033"},"PeriodicalIF":0.0,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748514/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054443","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}

{"title":"Exploring age and gender disparities in cardiometabolic phenotypes and lipidomic signatures among Chinese adults: a nationwide cohort study.","authors":"Xiaojing Jia, Hong Lin, Ruizhi Zheng, Shuangyuan Wang, Yilan Ding, Chunyan Hu, Mian Li, Yu Xu, Min Xu, Guixia Wang, Lulu Chen, Tianshu Zeng, Ruying Hu, Zhen Ye, Lixin Shi, Qing Su, Yuhong Chen, Xuefeng Yu, Li Yan, Tiange Wang, Zhiyun Zhao, Guijun Qin, Qin Wan, Gang Chen, Meng Dai, Di Zhang, Bihan Qiu, Xiaoyan Zhu, Jie Zheng, Xulei Tang, Zhengnan Gao, Feixia Shen, Xuejiang Gu, Zuojie Luo, Yingfen Qin, Li Chen, Xinguo Hou, Yanan Huo, Qiang Li, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Jiajun Zhao, Yiming Mu, Shenghan Lai, Donghui Li, Weiguo Hu, Guang Ning, Weiqing Wang, Yufang Bi, Jieli Lu","doi":"10.1093/lifemeta/loae032","DOIUrl":"10.1093/lifemeta/loae032","url":null,"abstract":"<p><p>Understanding sex disparities in modifiable risk factors across the lifespan is essential for crafting individualized intervention strategies. We aim to investigate age-related sex disparity in cardiometabolic phenotypes in a large nationwide Chinese cohort. A total of 254,670 adults aged 40 years or older were selected from a population-based cohort in China. Substantial sex disparities in the prevalence of metabolic diseases were observed across different age strata, particularly for dyslipidemia and its components. Generalized additive models were employed to characterize phenotype features, elucidating how gender differences evolve with advancing age. Half of the 16 phenotypes consistently exhibited no sex differences, while four (high-density lipoprotein [HDL] cholesterol, apolipoprotein A1, diastolic blood pressure, and fasting insulin) displayed significant sex differences across all age groups. Triglycerides, apolipoprotein B, non-HDL cholesterol, and total cholesterol demonstrated significant age-dependent sex disparities. Notably, premenopausal females exhibited significant age-related differences in lipid levels around the age of 40-50 years, contrasting with the relatively stable associations observed in males and postmenopausal females. Menopause played an important but not sole role in age-related sex differences in blood lipids. Sleep duration also had an age- and sex-dependent impact on lipids. Lipidomic analysis and K-means clustering further revealed that 58.6% of the 263 measured lipids varied with sex and age, with sphingomyelins, cholesteryl esters, and triacylglycerols being the most profoundly influenced lipid species by the combined effects of age, sex, and their interaction. These findings underscore the importance of age consideration when addressing gender disparities in metabolic diseases and advocate for personalized, age-specific prevention and management.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"3 5","pages":"loae032"},"PeriodicalIF":0.0,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054449","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}

{"title":"Gut bacterial metabolism produces neuroactive steroids in pregnant women","authors":"Kelsey E Huus, Ruth E. Ley","doi":"10.1093/lifemeta/loae030","DOIUrl":"https://doi.org/10.1093/lifemeta/loae030","url":null,"abstract":"","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"114 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141822033","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}

{"title":"Potential therapeutic strategies for MASH: from preclinical to clinical development","authors":"Zhifu Xie, Yufeng Li, Long Cheng, Yidan Huang, Wanglin Rao, Honglu Shi, Jingya Li","doi":"10.1093/lifemeta/loae029","DOIUrl":"https://doi.org/10.1093/lifemeta/loae029","url":null,"abstract":"\u0000 Current treatment paradigms for metabolic dysfunction-associated steatohepatitis (MASH) are based primarily on dietary restrictions and the use of existing drugs, including anti-diabetic and anti-obesity medications. However, given the limited number of approved drugs specifically for MASH, recent efforts have focused on promising strategies that specifically target hepatic lipid metabolism, inflammation, fibrosis, or a combination of these processes. In this review, we examined the pathophysiology underlying the development of MASH in relation to recent advances in effective MASH therapy. Particularly, we analyzed the effects of lipogenesis inhibitors, nuclear receptor agonists, glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists, fibroblast growth factor mimetics, and combinatorial therapeutic approaches. We summarize these targets along with their preclinical and clinical candidates with the ultimate goal of optimizing the therapeutic prospects for MASH.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":" 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141671861","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}

{"title":"BAT-tling oxidative stress through BCAA catabolism.","authors":"Maria Delgado-Martin, Qiaoqiao Zhang, Lawrence Kazak","doi":"10.1093/lifemeta/loae028","DOIUrl":"10.1093/lifemeta/loae028","url":null,"abstract":"","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"3 5","pages":"loae028"},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054447","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}

{"title":"The <i>FTO</i> variant conferring enhanced UCP1 expression is linked to human migration out of Africa.","authors":"Nan Yin, Dan Zhang, Jiqiu Wang","doi":"10.1093/lifemeta/loae027","DOIUrl":"10.1093/lifemeta/loae027","url":null,"abstract":"","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"3 6","pages":"loae027"},"PeriodicalIF":0.0,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748519/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054441","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}

{"title":"Phytic acid-based nanomedicine against mTOR represses lipogenesis and immune response for metabolic dysfunction-associated steatohepatitis therapy.","authors":"Fenghua Xu, Shoujie Zhao, Yejing Zhu, Jun Zhu, Lingyang Kong, Huichen Li, Shouzheng Ma, Bo Wang, Yongquan Qu, Zhimin Tian, Junlong Zhao, Lei Liu","doi":"10.1093/lifemeta/loae026","DOIUrl":"10.1093/lifemeta/loae026","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatohepatitis (MASH) is one of the most common chronic liver diseases and is mainly caused by metabolic disorders and systemic inflammatory responses. Recent studies have indicated that the activation of the mammalian (or mechanistic) target of rapamycin (mTOR) signaling participates in MASH progression by facilitating lipogenesis and regulating the immune microenvironment. Although several molecular medicines have been demonstrated to inhibit the phosphorylation or activation of mTOR, their poor specificity and side effects limit their clinical application in MASH treatment. Phytic acid (PA), as an endogenous and natural antioxidant in the liver, presents significant anti-inflammatory and lipid metabolism-inhibiting functions to alleviate MASH. In this study, considering the unique phosphate-rich structure of PA, we developed a cerium-PA (CePA) nanocomplex by combining PA with cerium ions possessing phosphodiesterase activity. CePA intervened in the S2448 phosphorylation of mTOR through the occupation effect of phosphate groups, thereby inhibiting the inflammatory response and mTOR-sterol regulatory element-binding protein 1 (SREBP1) regulation axis. The <i>in vivo</i> experiments suggested that CePA alleviated MASH progression and fat accumulation in high-fat diet-fed mice. Mechanistic studies validated that CePA exerts a liver-targeted mTOR repressive function, making it a promising candidate for MASH and other mTOR-related disease treatments.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"3 6","pages":"loae026"},"PeriodicalIF":0.0,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11748520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054329","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}