Life metabolism最新文献

Transporters in vitamin uptake and cellular metabolism: impacts on health and disease. 维生素摄取和细胞代谢中的转运体：对健康和疾病的影响。

Life metabolism Pub Date : 2025-03-10 eCollection Date: 2025-06-01 DOI: 10.1093/lifemeta/loaf008

Yaxuan Yuan, Ligong Chen

{"title":"Transporters in vitamin uptake and cellular metabolism: impacts on health and disease.","authors":"Yaxuan Yuan, Ligong Chen","doi":"10.1093/lifemeta/loaf008","DOIUrl":"https://doi.org/10.1093/lifemeta/loaf008","url":null,"abstract":"Vitamins are vital nutrients essential for metabolism, functioning as coenzymes, antioxidants, and regulators of gene expression. Their absorption and metabolism rely on specialized transport proteins that ensure bioavailability and cellular utilization. Water-soluble vitamins, including B-complex and vitamin C, are transported by solute carrier (SLC) family proteins and ATP-binding cassette (ABC) transporters for efficient uptake and cellular distribution. Fat-soluble vitamins (A, D, E, and K) rely on lipid-mediated pathways through proteins like scavenger receptor class B type I (SR-BI), CD36, and Niemann-Pick C1-like 1 (NPC1L1), integrating their absorption with lipid metabolism. Defective vitamin transporters are associated with diverse metabolic disorders, including neurological, hematological, and mitochondrial diseases. Advances in structural and functional studies of vitamin transporters highlight their tissue-specific roles and regulatory mechanisms, shedding light on their impact on health and disease. This review emphasizes the significance of vitamin transporters and their potential as therapeutic targets for deficiencies and related chronic conditions.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"4 3","pages":"loaf008"},"PeriodicalIF":0.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12121362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183635","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

Intermittent fasting promotes HFSC death to inhibit hair growth. 间歇性禁食促进HFSC死亡，抑制头发生长。

Life metabolism Pub Date : 2025-02-19 eCollection Date: 2025-04-01 DOI: 10.1093/lifemeta/loaf006

Abigail Benvie, Valerie Horsley

引用次数: 0

Development of cyclopeptide inhibitors specifically disrupting FXR-coactivator interaction in the intestine as a novel therapeutic strategy for MASH. 环肽抑制剂在肠道中特异性破坏fxr -辅激活物相互作用的发展作为一种新的治疗MASH的策略。

Life metabolism Pub Date : 2025-02-08 eCollection Date: 2025-04-01 DOI: 10.1093/lifemeta/loaf004

Yazhou Li, Tingying Jiao, Xi Cheng, Lu Liu, Mengjiao Zhang, Jian Li, Jue Wang, Shulei Hu, Cuina Li, Tao Yu, Yameng Liu, Yangtai Li, Yu Zhang, Chuying Sun, Jina Sun, Jiang Wang, Cen Xie, Hong Liu

{"title":"Development of cyclopeptide inhibitors specifically disrupting FXR-coactivator interaction in the intestine as a novel therapeutic strategy for MASH.","authors":"Yazhou Li, Tingying Jiao, Xi Cheng, Lu Liu, Mengjiao Zhang, Jian Li, Jue Wang, Shulei Hu, Cuina Li, Tao Yu, Yameng Liu, Yangtai Li, Yu Zhang, Chuying Sun, Jina Sun, Jiang Wang, Cen Xie, Hong Liu","doi":"10.1093/lifemeta/loaf004","DOIUrl":"https://doi.org/10.1093/lifemeta/loaf004","url":null,"abstract":"Intestinal farnesoid X receptor (FXR) antagonists have been proven to be efficacious in ameliorating metabolic diseases, particularly for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). All the reported FXR antagonists target to the ligand-binding pocket (LBP) of the receptor, whereas antagonist acting on the non-LBP site of nuclear receptor (NR) is conceived as a promising strategy to discover novel FXR antagonist. Here, we have postulated the hypothesis of antagonizing FXR by disrupting the interaction between FXR and coactivators, and have successfully developed a series of macrocyclic peptides as FXR antagonists based on this premise. The cyclopeptide DC646 not only exhibits potent inhibitory activity of FXR, but also demonstrates a high degree of selectivity towards other NRs. Moreover, cyclopeptide DC646 has high potential therapeutic benefit for the treatment of MASH in an intestinal FXR-dependent manner, along with a commendable safety profile. Mechanistically, distinct from other known FXR antagonists, cyclopeptide DC646 specifically binds to the coactivator binding site of FXR, which can block the coactivator recruitment, reducing the circulation of intestine-derived ceramides to the liver, and promoting the release of glucagon-like peptide-1 (GLP-1). Overall, we identify a novel cyclopeptide that targets FXR-coactivator interaction, paving the way for a new approach to treating MASH with FXR antagonists.","PeriodicalId":74074,"journal":{"name":"Life metabolism","volume":"4 2","pages":"loaf004"},"PeriodicalIF":0.0,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11992618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059897","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

PCSK9 V474I germline variant drives breast cancer metastasis. PCSK9 V474I种系变异驱动乳腺癌转移

Life metabolism Pub Date : 2025-01-04 eCollection Date: 2025-02-01 DOI: 10.1093/lifemeta/loae041

Hai Wang, Zhiming Shao

引用次数: 0

Glucose-6-phosphate dehydrogenase regulates mitophagy by maintaining PINK1 stability. 葡萄糖-6-磷酸脱氢酶通过维持PINK1的稳定性来调节线粒体自噬。

Life metabolism Pub Date : 2024-12-13 eCollection Date: 2025-02-01 DOI: 10.1093/lifemeta/loae040

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

{"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":"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 per se 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.","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}

引用次数: 0

Biphasic glucose-stimulated insulin secretion over decades: a journey from measurements and modeling to mechanistic insights. 几十年来，双相葡萄糖刺激胰岛素分泌：从测量和建模到机制见解的旅程。

Life metabolism Pub Date : 2024-11-19 eCollection Date: 2025-02-01 DOI: 10.1093/lifemeta/loae038

Xiaohong Peng, Kai Wang, Liangyi Chen

{"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":"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 in vivo 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.","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}

引用次数: 0

Chronic cold exposure reprograms feeding-regulated LPL activity in white adipose tissues through hepatic ANGPTL3 and ANGPTL8. 慢性冷暴露通过肝脏ANGPTL3和ANGPTL8重新编程摄食调节的白色脂肪组织中的LPL活性。

Life metabolism Pub Date : 2024-10-16 eCollection Date: 2025-02-01 DOI: 10.1093/lifemeta/loae037

Yiliang Zhang, Shengyang Zhou, Runming Zhao, Yingzhen Huang, Yan Wang

引用次数: 0

The deuterated glucose insulin tolerance test: a new tool to delineate insulin-stimulated glucose uptake from suppression of endogenous glucose production. 氘化葡萄糖胰岛素耐量试验：通过抑制内源性葡萄糖产生来描述胰岛素刺激的葡萄糖摄取的新工具。

Life metabolism Pub Date : 2024-10-03 eCollection Date: 2025-02-01 DOI: 10.1093/lifemeta/loae036

Christian A Unger, Marion C Hope, Michael Chase Kettering, Cassidy E Socia, Barton C Rice, Darya S Niamira, William E Cotham, Reilly T Enos

引用次数: 0

CIDEC/FSP27 exacerbates obesity-related abdominal aortic aneurysm by promoting perivascular adipose tissue inflammation. CIDEC/FSP27通过促进血管周围脂肪组织炎症加重肥胖相关性腹主动脉瘤。

Life metabolism Pub Date : 2024-09-18 eCollection Date: 2025-02-01 DOI: 10.1093/lifemeta/loae035

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

{"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":"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 Fsp27 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 Cidec 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.","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}

引用次数: 0

Soy peptide as an anecdote to undernutrition. 大豆肽作为营养不良的轶事。

Life metabolism Pub Date : 2024-08-21 eCollection Date: 2024-10-01 DOI: 10.1093/lifemeta/loae034

Mark P Mattson

引用次数: 0