Life metabolismPub Date : 2024-08-02eCollection Date: 2024-10-01DOI: 10.1093/lifemeta/loae032
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
{"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}
Life metabolismPub Date : 2024-07-06DOI: 10.1093/lifemeta/loae029
Zhifu Xie, Yufeng Li, Long Cheng, Yidan Huang, Wanglin Rao, Honglu Shi, Jingya Li
{"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}
Life metabolismPub Date : 2024-06-22eCollection Date: 2024-12-01DOI: 10.1093/lifemeta/loae027
Nan Yin, Dan Zhang, Jiqiu Wang
{"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}
Life metabolismPub Date : 2024-06-18eCollection Date: 2024-12-01DOI: 10.1093/lifemeta/loae026
Fenghua Xu, Shoujie Zhao, Yejing Zhu, Jun Zhu, Lingyang Kong, Huichen Li, Shouzheng Ma, Bo Wang, Yongquan Qu, Zhimin Tian, Junlong Zhao, Lei Liu
{"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}
{"title":"Immuno-electron microscopy localizes Caenorhabditis elegans vitellogenins along the classic exocytosis route","authors":"Chao Zhai, Nan Zhang, Xixia Li, Xue-Ke Tan, Fei Sun, Meng-Qiu Dong","doi":"10.1093/lifemeta/loae025","DOIUrl":"https://doi.org/10.1093/lifemeta/loae025","url":null,"abstract":"\u0000 Vitellogenins (VITs) are the most abundant proteins in adult hermaphrodite Caenorhabditis elegans. VITs are synthesized in the intestine, secreted to the pseudocoelom, matured into yolk proteins, and finally deposited in oocytes as nutrients for progeny developme nt. How VITs are secreted out of the intestine remains unclear. Using immuno-electron microscopy (immuno-EM), we localize intestinal VITs along an exocytic pathway consisting of the rough endoplasmic reticulum (ER), the Golgi, and the lipid bilayer-bounded VIT vesicles (VVs). This suggests that the classic exocytotic pathway mediates the secretion of VITs from the intestine to the pseudocoelom. We also show that pseudocoelomic yolk patches (PYPs) are membrane-less and amorphous. The different VITs/yolk proteins are packed as a mixture into the above structures. The size of VVs can vary with the VIT levels and the age of the worm. On adult day 2 (AD 2), intestinal VVs (~200 nm in diameter) are smaller than gonadal yolk organelles (YOs, ~500 nm in diameter). VVs, PYPs, and YOs share a uniform medium electron density by conventional EM. The morphological profiles documented in this study serve as a reference for future studies of VITs/yolk proteins.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"3 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141346708","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}
Life metabolismPub Date : 2024-06-13DOI: 10.1093/lifemeta/loae023
H. Demagny, A. Perino, Kristina Schoonjans
{"title":"Protecting liver health with microbial-derived succinylated bile acids","authors":"H. Demagny, A. Perino, Kristina Schoonjans","doi":"10.1093/lifemeta/loae023","DOIUrl":"https://doi.org/10.1093/lifemeta/loae023","url":null,"abstract":"","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141347959","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}
Life metabolismPub Date : 2024-06-07DOI: 10.1093/lifemeta/loae024
Peter U Amadi, Da-wei Zhang
{"title":"Cholesin, a new hormone bridges intestinal cholesterol absorption and hepatic synthesis","authors":"Peter U Amadi, Da-wei Zhang","doi":"10.1093/lifemeta/loae024","DOIUrl":"https://doi.org/10.1093/lifemeta/loae024","url":null,"abstract":"","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":" 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141372758","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}