Life metabolism最新文献

{"title":"<i>PCSK9</i> V474I germline variant drives breast cancer metastasis.","authors":"Hai Wang, Zhiming Shao","doi":"10.1093/lifemeta/loae041","DOIUrl":"10.1093/lifemeta/loae041","url":null,"abstract":"","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"4 1","pages":"loae041"},"PeriodicalIF":0.0,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054451","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":"Glucose-6-phosphate dehydrogenase regulates mitophagy by maintaining PINK1 stability.","authors":"Yik-Lam Cho, Hayden Weng Siong Tan, Jicheng Yang, Basil Zheng Mian Kuah, Nicole Si Ying Lim, Naiyang Fu, Boon-Huat Bay, Shuo-Chien Ling, Han-Ming Shen","doi":"10.1093/lifemeta/loae040","DOIUrl":"10.1093/lifemeta/loae040","url":null,"abstract":"<p><p>Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme in the pentose phosphate pathway (PPP) in glycolysis. Glucose metabolism is closely implicated in the regulation of mitophagy, a selective form of autophagy for the degradation of damaged mitochondria. The PPP and its key enzymes such as G6PD possess important metabolic functions, including biosynthesis and maintenance of intracellular redox balance, while their implication in mitophagy is largely unknown. Here, via a whole-genome CRISPR-Cas9 screening, we identified that G6PD regulates PINK1 (phosphatase and tensin homolog [PTEN]-induced kinase 1)-Parkin-mediated mitophagy. The function of G6PD in mitophagy was verified via multiple approaches. G6PD deletion significantly inhibited mitophagy, which can be rescued by G6PD reconstitution. Intriguingly, while the catalytic activity of G6PD is required, the known PPP functions <i>per se</i> are not involved in mitophagy regulation. Importantly, we found a portion of G6PD localized at mitochondria where it interacts with PINK1. G6PD deletion resulted in an impairment in PINK1 stabilization and subsequent inhibition of ubiquitin phosphorylation, a key starting point of mitophagy. Finally, we found that G6PD deletion resulted in lower cell viability upon mitochondrial depolarization, indicating the physiological function of G6PD-mediated mitophagy in response to mitochondrial stress. In summary, our study reveals a novel role of G6PD as a key positive regulator in mitophagy, which bridges several important cellular processes, namely glucose metabolism, redox homeostasis, and mitochondrial quality control.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"4 1","pages":"loae040"},"PeriodicalIF":0.0,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054456","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":"Biphasic glucose-stimulated insulin secretion over decades: a journey from measurements and modeling to mechanistic insights.","authors":"Xiaohong Peng, Kai Wang, Liangyi Chen","doi":"10.1093/lifemeta/loae038","DOIUrl":"10.1093/lifemeta/loae038","url":null,"abstract":"<p><p>Glucose-stimulated insulin release from pancreatic β-cells is critical for maintaining blood glucose homeostasis. An abrupt increase in blood glucose concentration evokes a rapid and transient rise in insulin secretion followed by a prolonged, slower phase. A diminished first phase is one of the earliest indicators of β-cell dysfunction in individuals predisposed to develop type 2 diabetes. Consequently, researchers have explored the underlying mechanisms for decades, starting with plasma insulin measurements under physiological conditions and advancing to single-vesicle exocytosis measurements in individual β-cells combined with molecular manipulations. Based on a chain of evidence gathered from genetic manipulation to <i>in vivo</i> mouse phenotyping, a widely accepted theory posits that distinct functional insulin vesicle pools in β-cells regulate biphasic glucose-stimulated insulin secretion (GSIS) via activation of different metabolic signal pathways. Recently, we developed a high-resolution imaging technique to visualize single vesicle exocytosis from β-cells within an intact islet. Our findings reveal that β-cells within the islet exhibit heterogeneity in their secretory capabilities, which also differs from the heterogeneous Ca²⁺ signals observed in islet β-cells in response to glucose stimulation. Most importantly, we demonstrate that biphasic GSIS emerges from the interactions among α-, β-, and δ-cells within the islet and is driven by a small subset of hypersecretory β-cells. Finally, we propose that a shift from reductionism to holism may be required to fully understand the etiology of complex diseases such as diabetes.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"4 1","pages":"loae038"},"PeriodicalIF":0.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054452","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":"Chronic cold exposure reprograms feeding-regulated LPL activity in white adipose tissues through hepatic ANGPTL3 and ANGPTL8.","authors":"Yiliang Zhang, Shengyang Zhou, Runming Zhao, Yingzhen Huang, Yan Wang","doi":"10.1093/lifemeta/loae037","DOIUrl":"10.1093/lifemeta/loae037","url":null,"abstract":"<p><p>Graphical Abstract Lipoprotein lipase (LPL) mediates peripheral tissue triglyceride (TG) uptake. Hepatic ANGPTL3 (A3) and ANGPTL8 (A8) form a complex and inhibit LPL activity in the white adipose tissue (WAT) via systematic circulation. ANGPTL4 (A4) is expressed in WAT and inhibits LPL activity locally. Feeding increases hepatic A8 expression and increases its inhibition for WAT LPL activity together with A3, while feeding suppresses WAT A4 expression and releases its inhibition on LPL. At room temperature, the feeding-suppressed A4 overrides the feeding-increased A3/A8, resulting in increased LPL activity in WAT by food intake. Browning improves hepatic insulin sensitivity and increases postprandial A8 expression. The feeding-increased A3/A8 overrides the feeding-suppressed A4, resulting in suppressed LPL activity in WAT by food intake. This reprogrammed LPL regulation plays an important role in reprogramming TG metabolism during adipose tissue browning.</p>","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"4 1","pages":"loae037"},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11770819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054453","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 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}