Current opinion in lipidology最新文献

{"title":"Editorial introduction.","authors":"","doi":"10.1097/MOL.0000000000001037","DOIUrl":"10.1097/MOL.0000000000001037","url":null,"abstract":"","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":"37 2","pages":"v"},"PeriodicalIF":4.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond cellular distress: reframing GDF15 as a lipid-sensitive metabolic signal.","authors":"Dongdong Wang, Logan K Townsend, Gregory R Steinberg","doi":"10.1097/MOL.0000000000001025","DOIUrl":"10.1097/MOL.0000000000001025","url":null,"abstract":"<p><strong>Purpose of review: </strong>Growth differentiation factor-15 (GDF15) is widely described as a hormone that conveys somatic distress to the brain, yet this framework does not explain why GDF15 is elevated in many common metabolic states. Recent work shows that GDF15 rises most consistently when fatty acid availability exceeds mitochondrial and endoplasmic reticulum capacity. This review synthesizes emerging evidence that positions GDF15 as an endocrine sensor of lipid load rather than a general stress signal.</p><p><strong>Recent findings: </strong>Across acute dietary lipid exposure, endogenous lipolysis during fasting, chronic overnutrition, ketogenic feeding, and mitochondrial dysfunction, free fatty acids activate lipid-sensitive transcriptional pathways that induce GDF15 expression in kidney, liver, intestine, and adipose tissue macrophages. Once elevated, GDF15 engages hindbrain glial-cell-derived neurotrophic factor family receptor α-like (GFRAL) signaling to increase sympathetic outflow, promote whole-body fatty acid oxidation, redistribute lipid burden, and improve metabolic flexibility. These effects occur independently of reduced food intake and reflect coordinated actions across liver, adipose tissue, and skeletal muscle.</p><p><strong>Summary: </strong>Viewing GDF15 as a lipid-responsive hormonal signal reshapes our understanding of its physiological role and provides new insight into metabolic adaptations to lipid overload. This pattern suggests that GDF15 is part of a feedback system that attempts to match fatty acid oxidation with supply, analogous to how carbohydrate ingestion stimulates insulin to promote glucose oxidation and suppress hepatic glucose production to restore euglycemia. Within this framework, individual tissues respond in complementary ways to reduce lipid burden and maintain metabolic balance. Understanding this coordinated lipid-responsive network highlights opportunities to target the GDF15 pathway in disorders characterized by impaired fatty acid handling including obesity, type 2 diabetes, cardiovascular disease, cancer cachexia and metabolic dysfunction-associated steatotic liver disease (MASLD).</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"45-51"},"PeriodicalIF":4.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147321405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic insights from Greenland: when geography, history and genomics converge.","authors":"Robert A Hegele","doi":"10.1097/MOL.0000000000001038","DOIUrl":"https://doi.org/10.1097/MOL.0000000000001038","url":null,"abstract":"","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":"37 2","pages":"27-29"},"PeriodicalIF":4.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147364427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of mRNA and protein isoforms in lipoprotein metabolism and how to modulate them.","authors":"Kelly M Martinovich, Jessica M Cale, May T Aung-Htut","doi":"10.1097/MOL.0000000000001026","DOIUrl":"10.1097/MOL.0000000000001026","url":null,"abstract":"<p><strong>Purpose of review: </strong>More than 95% of human genes undergo alternative pre-mRNA processing based on cell type, developmental stages, and environmental stimuli, among other factors. Not all alternatively spliced mRNAs are translated to proteins, and some of the noncoding mRNA isoforms play vital roles in cellular homeostasis. This review summarizes protein coding and noncoding RNA isoforms reported for key genes involved in lipoprotein metabolism, and emerging technologies that can be exploited to specifically induce a desired isoform.</p><p><strong>Recent findings: </strong>As sequencing technologies become more accessible, more variations in gene transcripts are being detected. Publicly available databases collate these as they arise, but not all of them are captured. Additionally, the function, if any, of many of these alternatively spliced transcripts is currently unknown. Novel strategies to investigate specific transcripts are also continuously evolving.</p><p><strong>Summary: </strong>Most human genes are alternatively spliced, generating various mRNAs and protein isoforms. Any cis or trans factors that alter the balance of these isoforms can have deleterious effects. The fundamental knowledge on the role of each isoform in maintaining cellular health is currently lacking. Emerging technologies which allow modulation of natural mRNA splicing can be used to further our understanding of natural isoform expression and function.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"52-57"},"PeriodicalIF":4.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12978708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultra-processed foods and CKD: a review of evidence, limitations, and future directions.","authors":"Giulia Barbieri, Cristina Valle-Hita, Essi Hantikainen","doi":"10.1097/MOL.0000000000001020","DOIUrl":"10.1097/MOL.0000000000001020","url":null,"abstract":"<p><strong>Purpose of review: </strong>To critically examine the emerging evidence linking ultra-processed food (UPF) consumption to chronic kidney disease (CKD), with a particular focus on prevention strategies, biological mechanisms, and implications for dietary guidelines and public health policy.</p><p><strong>Recent findings: </strong>Recent systematic reviews and meta-analyses consistently report a positive association between high UPF consumption and CKD risk. Mechanistic insights suggest roles for food additives, altered nutrient bioavailability, and inflammatory pathways, while omics-based studies offer preliminary biomarker candidates. The KDIGO 2024 guidelines now emphasize dietary interventions, including reduced UPF consumption, as a core component of CKD management.</p><p><strong>Summary: </strong>The findings support limiting UPF consumption as part of CKD prevention strategies. Nonetheless, the evidence base is largely derived from overlapping observational studies, with limited original research published in the considered timeframe. Moreover, the scarcity of recent original studies, methodological inconsistencies in UPF classification and CKD outcome definitions, highlight the urgent need for further research and standardization of approaches. Integrating precision nutrition and validated biomarkers into nephrology could enhance individualized dietary recommendations and public health interventions.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":"37 1","pages":"7-13"},"PeriodicalIF":4.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Harnessing dysglycaemia heterogeneity for precision type 2 diabetes prevention.","authors":"Suyi Xie, Jordi Merino","doi":"10.1097/MOL.0000000000001018","DOIUrl":"10.1097/MOL.0000000000001018","url":null,"abstract":"<p><strong>Purpose of review: </strong>Type 2 diabetes (T2D) is a heterogeneous, progressive metabolic disease and a major contributor to cardiovascular disease worldwide. Current prevention strategies, centred on population-level lifestyle recommendations, have had limited success, highlighting the need for more comprehensive approaches that account for interindividual variation in intervention response.</p><p><strong>Recent findings: </strong>Although discrete T2D subtypes using genomics or clinical variables have been proposed for targeted diabetes prevention and care strategies, emerging evidence supports a more dynamic view of heterogeneity as a continuous spectrum of metabolic dysfunction. Continuous glucose monitoring and multiomics profiling have shown promises in detecting early metabolic dysfunction in individuals with normal glycemia.</p><p><strong>Summary: </strong>In this review, we synthesize advances in modelling T2D phenotypic continuum and highlight how emerging technologies, including continuous glucose monitoring and multiomics profiling, can detect early metabolic dysregulation. We also discuss methodological challenges, such as the need for standardized deep phenotyping, robust analytic frameworks, and inclusion of diverse populations to ensure equity in translation. Finally, we outline future directions for translating these insights into scalable, mechanism-informed interventions that address glycaemic progression from subclinical changes to more advanced forms of the disease.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"1-6"},"PeriodicalIF":4.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145400078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The current landscape of prospective proteomics research into dementia using blood-based samples.","authors":"Josefine Tvermoes Meineche, Michael Wierer, Majken Karoline Jensen","doi":"10.1097/MOL.0000000000001019","DOIUrl":"10.1097/MOL.0000000000001019","url":null,"abstract":"<p><strong>Purpose of review: </strong>Well conducted, prospective, blood-based biomarker studies on dementia risk are growing, providing valuable insights into disease mechanisms that precede clinical symptoms. These investigations are crucial for advancing our understanding of dementia pathology and identifying early biological changes.</p><p><strong>Recent findings: </strong>Emerging evidence shows that proteins detected in peripheral tissues and the circulatory system can also play a role in neurological diseases. Both neuronal and nonbrain-specific proteins have been associated with dementia prior to symptom onset, highlighting the complex and multisystem nature of disease development. Of the 11 studies included in this review that focused on prospective studies of dementia that applied plasma proteomics, 36 proteins were identified in at least two independent cohorts, suggesting that blood-based proteomics detects consistent protein levels that may be altered years before dementia diagnosis.</p><p><strong>Summary: </strong>Blood-based biomarkers hold promise for early diagnosis, patient stratification, and mechanistic research in dementia. The observed overlap in protein profiles across studies suggests we are beginning to uncover systemic biological differences that contribute to disease progression.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":" ","pages":"14-26"},"PeriodicalIF":4.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145451214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation and atherosclerotic cardiovascular disease: where do we go from here?","authors":"Ori Waksman, Ron Waksman","doi":"10.1097/MOL.0000000000001009","DOIUrl":"10.1097/MOL.0000000000001009","url":null,"abstract":"<p><strong>Purpose of review: </strong>Low-grade systemic inflammation, as determined by high-sensitivity C-Reactive Protein (hsCRP), plays a significant role in the progression and development of atherosclerotic cardiovascular disease (ASCVD) and is recognized as a risk enhancer for increased incidence of major adverse cardiovascular events (MACE). (In 2024, the US Food and Drug Administration approved colchicine, as the first anti-inflammatory agent for secondary cardiovascular prevention. While this step signified a translational milestone, recent neutral colchicine trials such as CLEAR- SYNERGY, have reignited controversy regarding the overall efficacy of colchicine, and the need for alternative anti-inflammatory therapies. As the understanding of inflammation's role in atherosclerosis grows, questions persist about the best management strategies and future therapeutic options. This review aims to provide an updated summary that includes insights from recent key trials, explores investigational anti-inflammatory treatments, and discusses considerations for future trial designs.</p><p><strong>Recent findings: </strong>This review will encompass recent trials involving colchicine, IL-1 antagonists, and interluekin-6 Inhibitors.</p><p><strong>Summary: </strong>In this review, we will discuss mechanisms of inflammation as they pertain to ASCVD, significant contemporary trials, novel anti-inflammatory therapies, and considerations for future trial designs.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":"36 6","pages":"326-332"},"PeriodicalIF":4.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Future of angiopoietin-like protein 3 inhibitors as a therapeutic agent.","authors":"Nicholas A Marston, André Zimerman","doi":"10.1097/MOL.0000000000001013","DOIUrl":"10.1097/MOL.0000000000001013","url":null,"abstract":"<p><strong>Purpose of review: </strong>Triglyceride-rich lipoproteins (TRLs) and LDL remain major drivers of atherosclerotic cardiovascular disease, and angiopoietin-like protein 3 (ANGPTL3) has emerged as a promising target to lower both triglycerides and LDL cholesterol (LDL-C). This review provides an overview on ANGPTL3 inhibition, including genetic insights and clinical evidence, and examines patient groups in which therapies may be particularly well suited to reduce residual cardiovascular risk.</p><p><strong>Recent findings: </strong>Genetic studies have shown that carriers of ANGPTL3 loss-of-function variants exhibit lower levels of triglycerides and LDL-C, and a reduced cardiovascular risk. Evinacumab, a monoclonal antibody targeting ANGPTL3, lowers LDL-C by approximately 50% in patients with homozygous familial hypercholesterolemia (HoFH), in whom traditional lipid-lowering therapies are largely ineffective. In patients with mixed dyslipidemia, small interfering RNAs (e.g. zodasiran and solbinsiran) and antisense oligonucleotides (e.g. vupanorsen) achieve approximately 60% triglyceride and 20% LDL-C lowering, with the small interfering RNAs having a generally favorable safety profile.</p><p><strong>Summary: </strong>ANGPTL3 inhibition offers an LDL receptor-independent means to lower atherogenic particles spanning from TRLs to LDL, complementing traditional lipid-lowering therapies. Evinacumab is practice-changing in HoFH, and RNA agents may soon broaden applicability to patients with mixed dyslipidemia and residual cardiovascular risk, pending cardiovascular outcomes trials.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":"36 6","pages":"285-291"},"PeriodicalIF":4.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evolving guidelines on lipoprotein(a).","authors":"Michael B Boffa, Marlys L Koschinsky, Robert A Hegele","doi":"10.1097/MOL.0000000000001016","DOIUrl":"10.1097/MOL.0000000000001016","url":null,"abstract":"<p><strong>Purpose of review: </strong>Elevated plasma lipoprotein(a) [Lp(a)] is a causal and independent risk factor for atherosclerotic cardiovascular disease and an emerging therapeutic target. Over the past 15 years, many medical bodies from around the world have released scientific statements and clinical guidelines regarding Lp(a). This review tracks how recommendations on Lp(a) have evolved over this timeframe.</p><p><strong>Recent findings: </strong>Powerful studies demonstrating the independent association of elevated Lp(a) in large numbers of patients have been published. The data allowed a more precise formulation of risk categories for Lp(a) levels and of models for how a given level of Lp(a) in a moderate-risk to high-risk primary prevention patient might inform management of modifiable risk factors such as LDL cholesterol. Guidelines and statements have increasingly recommended universal screening for elevated Lp(a) and have identified elevated Lp(a) as a risk-enhancing or amplifying factor. However, some gaps and inconsistencies remain.</p><p><strong>Summary: </strong>Ongoing cardiovascular outcomes trials of potent Lp(a)-lowering therapies will inform clinical use of Lp(a) in the future. Presently, consensus is building for measurement of Lp(a) in all adults and for incorporation of Lp(a) levels into clinical decision-making for prevention of cardiovascular disease. However, caution is warranted as the evidence base underlying this consensus has several important missing pieces.</p>","PeriodicalId":11109,"journal":{"name":"Current opinion in lipidology","volume":"36 6","pages":"300-309"},"PeriodicalIF":4.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}