Journal of Lipid Research最新文献

{"title":"Setting the curve: the biophysical properties of lipids in mitochondrial form and function.","authors":"Kailash Venkatraman, Christopher T Lee, Itay Budin","doi":"10.1016/j.jlr.2024.100643","DOIUrl":"10.1016/j.jlr.2024.100643","url":null,"abstract":"<p><p>Mitochondrial membranes are defined by their diverse functions, complex geometries, and unique lipidomes. In the inner mitochondrial membrane, highly curved membrane folds known as cristae house the electron transport chain and are the primary sites of cellular energy production. The outer mitochondrial membrane is flat by contrast, but is critical for the initiation and mediation of processes key to mitochondrial physiology: mitophagy, interorganelle contacts, fission and fusion dynamics, and metabolite transport. While the lipid composition of both the inner mitochondrial membrane and outer mitochondrial membrane have been characterized across a variety of cell types, a mechanistic understanding for how individual lipid classes contribute to mitochondrial structure and function remains nebulous. In this review, we address the biophysical properties of mitochondrial lipids and their related functional roles. We highlight the intrinsic curvature of the bulk mitochondrial phospholipid pool, with an emphasis on the nuances surrounding the mitochondrially-synthesized cardiolipin. We also outline emerging questions about other lipid classes - ether lipids, and sterols - with potential roles in mitochondrial physiology. We propose that further investigation is warranted to elucidate the specific properties of these lipids and their influence on mitochondrial architecture and function.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100643"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel odd-chain cyclopropane fatty acids: detection in a mammalian lipidome and uptake by hepatosplanchnic tissues.","authors":"Hany F Sobhi, Kelly E Mercer, Renny S Lan, Laxmi Yeruva, Gabriella A M Ten Have, Nicolaas E P Deutz, Brian D Piccolo, Jean Debédat, Lindsay M Pack, Sean H Adams","doi":"10.1016/j.jlr.2024.100632","DOIUrl":"10.1016/j.jlr.2024.100632","url":null,"abstract":"<p><p>Microbe-produced molecules (xenometabolites) found in foods or produced by gut microbiota are increasingly implicated in microbe-microbe and microbe-host communication. Xenolipids, in particular, are a class of metabolites for which the full catalog remains to be elaborated in mammalian systems. We and others have observed that cis-3,4-methylene-heptanoylcarnitine is a lipid derivative that is one of the most abundant medium-chain acylcarnitines in human blood, hypothesized to be a product of incomplete β-oxidation of one or more \"odd-chain\" long-chain cyclopropane fatty acids (CpFAs). We deduced two possible candidates, cis-11,12-methylene-pentadecanoic acid (cis-11,12-MPD) and cis-13,14-methylene-heptadecanoic acid (cis-13,14-MHD). Authentic standards were synthesized: cis-11-pentadecenoic acid and cis-13-heptadecenoic acid were generated (using Jones reagent) from cis-11-pentadecene-1-ol and cis-13-heptadecene-1-ol, respectively, and these were converted to CpFAs via a reaction involving diiodomethane. Using these standards in mass spectrometry analyses, we determined the presence/absence of cis-11,12-MPD and cis-13,14-MHD in archived piglet biospecimens. Both CpFAs were detected in rectal contents of sow and soy-fed piglets. Archived mass spectra were analyzed post hoc from a second independent study that used tissue-specific catheterization to monitor net metabolite flux in growing pigs. This confirmed the presence of both CpFAs in plasma and revealed a significant net uptake of the odd-chain CpFAs across the splanchnic tissue bed and liver. The results confirm that the novel xenolipids cis-11,12-MPD and cis-13,14-MHD can be components of the mammalian lipidome and are viable candidate precursors of cis-3,4-methylene-heptanoylcarnitine produced from partial β-oxidation in liver or other tissues.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100632"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11439845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modification in mitochondrial function is associated with the FADS1 variant and its interaction with alpha-linolenic acid-enriched diet-An exploratory study.","authors":"Maija Vaittinen, Mariana Ilha, Ratika Sehgal, Maria A Lankinen, Jyrki Ågren, Pirjo Käkelä, Kirsi A Virtanen, Markku Laakso, Ursula Schwab, Jussi Pihlajamäki","doi":"10.1016/j.jlr.2024.100638","DOIUrl":"10.1016/j.jlr.2024.100638","url":null,"abstract":"<p><p>Fatty acid desaturase (FADS1) variant-rs174550 strongly regulates polyunsaturated fatty acid (PUFA) biosynthesis. Additionally, the FADS1 is related to mitochondrial function. Thus, we investigated whether changes in mitochondrial function are associated with the genetic variation in FADS1 (rs174550) in human adipocytes isolated from individuals consuming diets enriched with either dietary alpha-linolenic (ALA) or linoleic acid (LA). Two cohorts of men homozygous for the genotype of FADS1 (rs174550) were studied: FADSDIET2 dietary intervention study with ALA- and LA-enriched diets and Kuopio Obesity Surgery study (KOBS), respectively. We could demonstrate that differentiated human adipose-derived stromal cells from subjects with the TT genotype had higher mitochondrial metabolism compared with subjects with the CC genotype of FADS1-rs174550 in the FADSDIET2. Responses to PUFA-enriched diets differed between the genotypes of FADS1-rs174550, showing that ALA, but not LA, -enriched diet stimulated mitochondrial metabolism more in subjects with the CC genotype when compared with subjects with the TT genotype. ALA, but not LA, proportion in plasma phospholipid fraction correlated positively with adipose tissue mitochondrial-DNA amount in subjects with the CC genotype of FADS1-rs174550 in the KOBS. These findings demonstrate that the FADS1-rs174550 is associated with modification in mitochondrial function in human adipocytes. Additionally, subjects with the CC genotype, when compared with the TT genotype, benefit more from the ALA-enriched diet, leading to enhanced energy metabolism in human adipocytes. Altogether, the FADS1-rs174550 could be a genetic marker to identify subjects who are most suitable to receive dietary PUFA supplementation, establishing also a personalized therapeutic strategy to improve mitochondrial function in metabolic diseases.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100638"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatty acid synthase inhibitor cerulenin hinders liver cancer stem cell properties through FASN/APP axis as novel therapeutic strategies.","authors":"Liang-Yun Chen, Dao-Sian Wu, Yao-An Shen","doi":"10.1016/j.jlr.2024.100660","DOIUrl":"10.1016/j.jlr.2024.100660","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) poses significant treatment challenges due to high postoperative recurrence rates and the limited effectiveness of targeted medications. Researchers have identified the unique metabolic profiles of cancer stem cells (CSCs) as the primary drivers of cancer recurrence, metastasis, and drug resistance. Therefore, to address the therapeutic conundrum, this study focused on rewinding metabolic reprogramming of CSCs as a novel therapeutic strategy. HCC CSCs exhibited elevated fatty acid (FA) metabolism compared with parental cells. To specifically target FA metabolism in CSCs, we utilized cerulenin, a fatty acid synthase (FASN) inhibitor. Surprisingly, cerulenin can diminish CSC-like characteristics, including stemness gene expression, spherogenicity, tumorigenicity, and metastatic potential. In addition, sorafenib, a multikinase inhibitor used as targeted therapy for advanced HCC, was employed in combination with cerulenin, demonstrating a great synergistic effect, particularly in CSCs. Importantly, our RNA sequencing analysis disclosed that the amyloid protein precursor (APP) is a crucial downstream effector of FASN in regulating CSC properties. We found that APP plays a crucial role in CSCs' characteristics that can be inhibited by cerulenin. By focusing on FA metabolism, this study identified the FASN/APP axis as a viable target to develop a more potent therapy strategy for advanced HCC.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100660"},"PeriodicalIF":5.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539133/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brown fat fuels the fire in fever.","authors":"Samantha J Krysa, Jonathan R Brestoff","doi":"10.1016/j.jlr.2024.100658","DOIUrl":"10.1016/j.jlr.2024.100658","url":null,"abstract":"<p><p>Fever is a host-pathogen defense mechanism in which the immune system drives a physiologic increase in core body temperature. For over 50 years, it has been known that the temperature of brown adipose tissue (BAT) is increased during the febrile response. However, recent studies suggested that the primary thermogenic protein Uncoupling protein 1 in brown adipocytes does not contribute to fever induction in mice, casting doubt about the functional contribution of BAT to fever. In a new set of studies, Li et al. (2024) provide compelling evidence that fatty acid oxidation is markedly increased in BAT in a Salmonella infection model of fever and strongly suggest that metabolic adaptation in BAT may play a critical role in the febrile response. This article re-opens the debate about how thermogenic and metabolic programs in BAT contribute to fever and raises new questions about whether BAT contributes to host defense against pathogens.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100658"},"PeriodicalIF":5.0,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"sEV-mediated lipid droplets transferred from bone marrow adipocytes promote ferroptosis and impair osteoblast function.","authors":"Weibo Huang, Feng Hua, Tong Su, Chenghao Zhou, Kangcheng Zhao, Dianwen Song","doi":"10.1016/j.jlr.2024.100657","DOIUrl":"10.1016/j.jlr.2024.100657","url":null,"abstract":"<p><p>Osteoporosis is linked to increased bone marrow adipocyte (BMAd) proliferation, which displaces bone-forming cells and alters the local environment. The impact of BMAd lipid droplets on bone health and osteoblast function remains unclear. This study investigates the interplay between BMAd-derived lipid droplets and osteoblast functionality, focusing on ferroptosis pathways. Osteoblast cultures were treated with conditioned media from adipocytes to simulate in vivo conditions. High-throughput mRNA sequencing and Western blot analysis were used to profile changes in gene expression and protein levels related to ferroptosis, oxidative phosphorylation, and osteogenic markers. Cellular assays assessed the direct impact of lipid droplets on osteoblast activity. Results showed that osteoblasts exposed to adipocyte-conditioned media had increased intracellular lipid droplet accumulation, upregulation of ferroptosis-related genes and proteins, and downregulation of oxidative phosphorylation and osteoblast differentiation markers. Treatment with ferroptosis inhibitors reversed the detrimental effects on osteoblasts, indicating the functional relevance of this pathway in osteoporosis. BMAd-derived lipid droplets contribute to osteoblast dysfunction through ferroptosis induction. Inhibiting ferroptosis could preserve osteoblast function and combat osteoporosis-related bone issues, suggesting that modulating lipid metabolism and redox balance in bone cells may be promising for future treatments.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100657"},"PeriodicalIF":5.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11535364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142348331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triglyceride-rich lipoproteins cholesterol, 10-years atherosclerotic cardiovascular disease risk, and risk of myocardial infarction and ischemic stroke.","authors":"Yi-Ping Jia, Jia-Min Wang, Jie-Qiong Lyu, Huan-Huan Yang, Meng-Yuan Miao, Xiaowen Wang, Zhong-Xiao Wan, Yan Zheng, Li-Qiang Qin, Fu-Rong Li, Guo-Chong Chen","doi":"10.1016/j.jlr.2024.100653","DOIUrl":"10.1016/j.jlr.2024.100653","url":null,"abstract":"<p><p>Triglyceride-rich lipoproteins cholesterol (TRLs-C) has been associated with atherosclerotic cardiovascular disease (ASCVD), even among individuals with low-density lipoprotein cholesterol in the targeted range. We assessed the associations of TRLs-C with myocardial infarction (MI) and ischemic stroke (IS) and compared the associations with those for other traditional lipids (i.e., triglycerides and non-high-density lipoprotein cholesterol [non-HDL-C]). Included were 327,899 participants from the UK Biobank who were free of MI or IS and did not receive lipid-lowering treatment at baseline. Ten-year risk for ASCVD was estimated by the Pooled Cohort Equations and was grouped as low (<7.5%), intermediate (7.5% to <20%), and high risk (≥20%). Multivariable Cox regression models were used to examine the associations of TRLs-C, triglycerides, and non-HDL-C with risk of MI and IS, overall and by the 10-years risk categories. During a median of 12.3 years of follow-up, 8,358 incident MI and 4,400 incident IS cases were identified. After multivariable adjustment, higher TRLs-C was associated with a higher risk of MI (p-trend <0.0001) but not IS (p-trend = 0.074), with similar associations for triglycerides and non-HDL-C. There were interactions between TRLs-C and 10-years ASCVD risk on risk of MI (p-interaction <0.0001) and IS (p-interaction = 0.0003). Hazard ratios (95% CIs) of MI comparing the highest with the lowest quartiles of TRLs-C were 2.10 (1.23-1.30) in the low-risk group, 1.52 (1.38-1.69) in the intermediate-risk group, and 1.22 (1.03-1.45) in the high-risk group. The corresponding estimates for IS were 1.24 (1.05-1.45), 0.94 (0.83-1.07), and 0.83 (0.67-1.04), respectively. Similar interactions with the 10-years ASCVD risk were observed for triglycerides and non-HDL-C on risk of MI and for triglycerides on risk of IS. Elevated levels of TRLs-C (or triglycerides or non-HDL-C) are associated with a higher risk of developing MI and IS (except non-HDL-C) predominantly among individuals who are typically classified as being low-risk. These findings may have implications for more detailed risk stratification and early intervention.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100653"},"PeriodicalIF":5.0,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a monoclonal antibody to study MARCH6, an E3 ligase that regulates proteins that control lipid homeostasis.","authors":"Shimeng Xu, Linda Donnelly, Daniel L Kober, Myra Mak, Arun Radhakrishnan","doi":"10.1016/j.jlr.2024.100650","DOIUrl":"10.1016/j.jlr.2024.100650","url":null,"abstract":"<p><p>Membrane-associated ring-CH-type finger 6 (MARCH6), also designated as TEB4 or RNF176, is an E3 ligase that is embedded in membranes of the endoplasmic reticulum where it ubiquitinates many substrate proteins to consign them to proteasome-mediated degradation. In recent years, MARCH6 has been identified as a key regulator of several metabolic pathways, including cholesterol and lipid droplet homeostasis, protein quality control, ferroptosis, and tumorigenesis. Despite its importance, there are currently no specific antibodies to detect and monitor MARCH6 levels in cultured cells and animals. Here, we address this deficiency by generating a monoclonal antibody that specifically detects MARCH6 in cultured cells of insect, mouse, hamster, and human origin, as well as in mouse tissues, with minimal cross-reactivity against other proteins. We then used this antibody to assess two properties of MARCH6. First, analysis of mouse tissues with this antibody revealed that the liver contained the highest levels of March6. Second, analysis of five different cell lines with this antibody showed that endogenous levels of MARCH6 are unchanged as the cellular content of cholesterol is varied. This reagent promises to be a useful tool in interrogating additional signaling roles of MARCH6.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100650"},"PeriodicalIF":5.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into the molecular changes of adipocyte dedifferentiation and its future research opportunities.","authors":"Mingheng Xue, Yunjun Liao, Wenqing Jiang","doi":"10.1016/j.jlr.2024.100644","DOIUrl":"10.1016/j.jlr.2024.100644","url":null,"abstract":"<p><p>Recent studies have challenged the traditional belief that mature fat cells are irreversibly differentiated and revealed they can dedifferentiate into fibroblast-like cells known as dedifferentiated fat (DFAT) cells. Resembling pluripotent stem cells, DFAT cells hold great potential as a cell source for stem cell therapy. However, there is limited understanding of the specific changes that occur following adipocyte dedifferentiation and the detailed regulation of this process. This review explores the epigenetic, genetic, and phenotypic alterations associated with DFAT cell dedifferentiation, identifies potential targets for clinical regulation and discusses the current applications and challenges in the field of DFAT cell research.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100644"},"PeriodicalIF":5.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11550672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Etomoxir: an old dog with new tricks.","authors":"Reagan M McGuffee, Kyle S McCommis, David A Ford","doi":"10.1016/j.jlr.2024.100604","DOIUrl":"10.1016/j.jlr.2024.100604","url":null,"abstract":"","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100604"},"PeriodicalIF":5.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11395757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}