Prostaglandins, leukotrienes, and essential fatty acids最新文献

{"title":"Dihomo-gamma-linolenic acid (DGLA) is inversely related to risk for cardiac death and cardiovascular events during 2 years follow-up after admission for an acute coronary syndrome","authors":"Dennis W.T. Nilsen ,&nbsp;Hildegunn Aarsetoey ,&nbsp;Volker Poenitz ,&nbsp;Trygve Brugger-Andersen ,&nbsp;William S. Harris ,&nbsp;Harry Staines ,&nbsp;Heidi Grundt","doi":"10.1016/j.plefa.2025.102684","DOIUrl":"10.1016/j.plefa.2025.102684","url":null,"abstract":"<div><h3>Background/Aim</h3><div>Dihomo-gamma-linolenic acid (DGLA) is derived from linoleic acid. Its presence in red blood cell (RBC) membranes is mainly due to metabolism and not diet. RBC DGLA was negatively associated with all-cause mortality during 7 years follow-up in patients admitted with an acute coronary syndrome (ACS). We now present its 2-year cardiovascular prognostic utility compared to other n-6 fatty acids (FAs).</div></div><div><h3>Methods</h3><div>A total of 139 females and 259 males with a mean age of 71.9 ± 13.0 years were admitted consecutively in this study. Stepwise Cox regression models, applying continuous values of DGLA weight percent (wt %) and quartiles, were fitted for the biomarkers with cardiac death and a combined cardiovascular (CV) endpoint consisting of cardiac death or myocardial infarction (MI) or stroke as the dependent variables.</div></div><div><h3>Results</h3><div>Cardiac death was recorded in 57 patients, and the composite CV endpoint in 144 patients, respectively. DGLA was negatively associated with both endpoints, each with a p-value of &lt;0.001 in univariate analysis. The hazard ratio (HR, per 1 wt % increase) remained significant after multivariable adjustment [cardiac death HR 0.51 (95 %CI 0.27–0.98), <em>p</em> = 0.042, and composite CV endpoint HR 0.61 (95 %CI 0.41–0.92), <em>p</em> = 0.017]. A similar pattern was obtained in ACS patients presenting with an acute MI at admission.</div><div>No association with any outcome was found with the other n-6 FAs [linoleic acid, arachidonic acid and adrenic acid].</div></div><div><h3>Conclusion</h3><div>Higher RBC DGLA predicts lower risk for cardiac death and cardiovascular outcomes at 2 years follow-up in ACS patients, whereas other n-6 FAs do not.</div><div>Clinical trial registration: ClinicalTrials.gov Identifier: NCT00521976</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"205 ","pages":"Article 102684"},"PeriodicalIF":3.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838384","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}

{"title":"Fatty acid metabolism in the placentae of gestational diabetes mellitus","authors":"Nikita Joshi,&nbsp;Sadhana Joshi","doi":"10.1016/j.plefa.2025.102682","DOIUrl":"10.1016/j.plefa.2025.102682","url":null,"abstract":"<div><div>The prevalence of gestational diabetes mellitus (GDM), a metabolic complication during pregnancy is increasing rapidly. It exerts various short and long term effects on the mother and the child. Nonetheless, the mechanisms underlying the pathophysiology of GDM are still not clear. Placenta is a key ‘programming’ agent and any impairment in placental structure and function may hamper the fetal growth and development. Omega-3 and omega-6 fatty acids are key nutrients involved in placental and fetal development. The fatty acids transport from maternal circulation towards the fetus depends on the fatty acid status of the mother, fatty acid metabolism of the placenta and placental transport of fatty acids. Alteration in any of these could influence the fatty acids transport towards the fetus thereby affecting the fetal brain development and leading to impairment in cognitive function in the off-spring. We propose a role for placental fatty acid metabolism in influencing fetal growth and development which in turn can have an impact on cognitive development of the offspring born to GDM women.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"205 ","pages":"Article 102682"},"PeriodicalIF":3.0,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143808231","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}

{"title":"HYPOTHESIS: Lipid-protecting disulfide bridges are the missing molecular link between ApoE4 and sporadic Alzheimer's disease in humans","authors":"Christopher E. Ramsden ,&nbsp;Roy G. Cutler ,&nbsp;Xiufeng Li ,&nbsp;Gregory S. Keyes","doi":"10.1016/j.plefa.2025.102681","DOIUrl":"10.1016/j.plefa.2025.102681","url":null,"abstract":"<div><div>As the principal lipid transporter in the human brain, apolipoprotein E (ApoE) is tasked with transport and protection of highly vulnerable lipids that are required to support and remodel neuronal membranes, in a process that is dependent on ApoE receptors. <em>APOE</em> allele variants that encode proteins differing only in the number of cysteine (Cys)-to-arginine (Arg) exchanges (ApoE2 [2 Cys], ApoE3 [1 Cys], ApoE4 [0 Cys]) comprise the strongest genetic risk factor for sporadic Alzheimer's disease (AD); however, the <em>specific</em> molecular feature(s) and resultant mechanisms that underlie these isoform-dependent effects are unknown. One signature feature of Cys is the capacity to form disulfide (Cys-Cys) bridges, which are required to form disulfide-linked dimers and multimers. Here we propose the overarching hypothesis that super-ability (for ApoE2), intermediate ability (for ApoE3) or inability (for ApoE4) to form lipid-protecting intermolecular disulfide bridges, is the central molecular determinant accounting for the disparate effects of <em>APOE</em> alleles on AD risk and amyloid-β and Tau pathologies in humans. We posit that presence and abundance of Cys in human ApoE3 and ApoE2 respectively, conceal and protect vulnerable lipids transported by ApoE from peroxidation by enabling formation of disulfide-linked homo- and heteromeric ApoE complexes. We thus propose that inability to form intermolecular disulfide bridges makes ApoE4-containing lipoproteins uniquely vulnerable to peroxidation and its downstream consequences. Consistent with our model, we found that brain-enriched polyunsaturated fatty acid-containing phospholipids induce disulfide-dependent dimerization and multimerization of ApoE3 and ApoE2 (but not ApoE4). By contrast, incubation with the peroxidation-resistant lipid DMPC or cholesterol alone had minimal effects on dimerization. These novel concepts and findings are integrated into our unifying model implicating peroxidation of ApoE-containing lipoproteins, with consequent ApoE receptor-ligand disruption, as initiating molecular events that ultimately lead to AD in humans.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"205 ","pages":"Article 102681"},"PeriodicalIF":3.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799315","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}

{"title":"LTB4 is converted into a potent human neutrophil NADPH oxidase activator via a receptor transactivation mechanism in which the BLT1 receptor activates the free fatty acid receptor 2","authors":"Yanling Wu ,&nbsp;Claes Dahlgren ,&nbsp;Huamei Forsman ,&nbsp;Martina Sundqvist","doi":"10.1016/j.plefa.2025.102680","DOIUrl":"10.1016/j.plefa.2025.102680","url":null,"abstract":"<div><div>The endogenous neutrophil chemoattractant leukotriene B₄ (LTB₄) is a biased signalling agonist that potently increases the intracellular concentration of free calcium ions ([Ca²⁺]_i), but alone is a weak activator of the neutrophil superoxide anion (O₂^-)-generating NADPH oxidase. However, in this study we show that an allosteric modulator of the free fatty acid 2 receptor (FFA2R) converts LTB₄ into a potent NADPH oxidase activating agonist. While an allosteric modulation of FFA2R was required for LTB₄ receptor 1 (BLT₁R)-mediated activation of the NADPH oxidase, the LTB₄-induced increase in [Ca²⁺]_i was not affected by the modulator. Thus, the biased BLT₁R signalling pattern was altered in the presence of the allosteric FFA2R modulator, being biased with a preference towards the signals that activate the NADPH oxidase relative to an increase in [Ca²⁺]_i. Both BLT₁R and FFA2R belong to the family of G protein-coupled receptors (GPCRs), and our results show that a communication between the activated BLT₁R and the allosterically modulated FFA2Rs generates signals that induce NADPH oxidase activity. This is consistent with a previously described receptor transactivation (crosstalk) model whereby the function of one neutrophil GPCR can be regulated by receptor downstream signals generated by another GPCR. Furthermore, the finding that an allosteric FFA2R modulator sensitises not only the response induced by orthosteric FFA2R agonists but also the response induced by LTB₄, violates the receptor restriction properties that normally define the selectivity of allosteric GPCR modulators.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"205 ","pages":"Article 102680"},"PeriodicalIF":3.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143790944","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":"Fatty acid synthase global inducible knockout does not alter brain fatty acid concentrations but attenuates cholesterol synthesis in the adult mouse","authors":"Drew R. Seeger,&nbsp;Peddanna Kotha,&nbsp;Svetlana A. Golovko,&nbsp;Eric J. Murphy,&nbsp;Mikhail Y. Golovko","doi":"10.1016/j.plefa.2025.102679","DOIUrl":"10.1016/j.plefa.2025.102679","url":null,"abstract":"<div><div>Fatty acid (FA) <em>de novo</em> synthesis, also called <em>de novo</em> lipogenesis (DNL), has a central role in peripheral energy storage and provides structural components for lipid membranes. However, less is known regarding its contribution to brain FA homeostasis. DNL is catalyzed by fatty acid synthase (FAS), which is a multifunctional enzyme expressed in all mammalian tissues. In the present study, we addressed, for the first time, the effect of FAS gene global conditional inducible knockout (<em>Fasn</em> KO) on the adult brain FA concentrations and lipid metabolism. We achieved a 67 % reduction in the brain FAS protein levels, with a significant reduction in total FA synthesis measured by ³H₂O incorporation into FA, which was lethal 10 days after gene recombination induction. However, the concentrations of all 44 FA molecular species assayed by LC-MS were unchanged in the brain. We also did not detect changes in the major proteins involved in FA synthesis regulation and remodeling, including peroxisome proliferator-activated receptor α (PPARα), PPARδ, FA desaturase-1, -2, and -3, and Stearoyl-CoA desaturase 1 but did observe a decrease in PPARɣ levels. In addition, brain cholesterol synthesis was significantly reduced in the <em>Fasn</em> KO brains. These data indicate that DNL is not required to maintain measured FA concentrations in the brain and that dietary FA and liver-derived pools might compensate for decreased brain DNL within the duration of the study. However, our data indicate a possible role of FAS in PPARɣ regulation and cholesterol metabolism in the adult brain.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"205 ","pages":"Article 102679"},"PeriodicalIF":3.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759005","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}

{"title":"Plasma oxylipins in children with sickle cell disease: Associations with biomarkers of inflammation and endothelial activation","authors":"BN Yamaja Setty ,&nbsp;Krishna Rao Maddipati ,&nbsp;Scott W Keith ,&nbsp;Ayako Shimada ,&nbsp;Pari Sheerer ,&nbsp;Robin E Miller","doi":"10.1016/j.plefa.2025.102670","DOIUrl":"10.1016/j.plefa.2025.102670","url":null,"abstract":"<div><div>Oxylipins are polyunsaturated fatty acid (PUFA)-derived inflammatory mediators, and include both pro-inflammatory (prostaglandins, thromboxane, leukotrienes), and pro-resolving (lipoxins, E-resolvins, D-resolvins, protectins, maresins) molecules. Sickle cell disease (SCD) is an inflammatory pathology. We profiled plasma oxylipins in SCD (<em>n</em> = 45) and control children (<em>n</em> = 24), and evaluated their associations with inflammatory biomarkers, and SCD clinical history. We demonstrated the presence of PGE2, TxB2, RvE2, RvD1, AT-RvD3, and numerous monohydroxy-PUFAs in both SCD and control plasma. Levels of TxB2, RvD1, 12-HETE, 5-HEPE, and 7-HDoHE were significantly increased in SCD. 12-HETE and 5-HEPE correlated positively with IL-6 and IL-1β, respectively, while 15-HETE negatively associated with soluble-ICAM-1. 7-HDoHE levels were significantly lower in children with a history of VOC and ACS compared to those without any clinical complications. Since RvD1 is a pro-resolving mediator, the observed increase in RvD1 in SCD may reflect a host mechanism attempting to mitigate disease-associated chronic inflammation by promoting resolution of inflammation.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"205 ","pages":"Article 102670"},"PeriodicalIF":3.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549276","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}

{"title":"The single-dose kinetics of [1–14C]-labelled EPA and DHA, administered to male rats as TAG, phosphatidylcholine (PC), and lyso-phosphatidylcholine (LPC), is structurally similar across lipid forms and can be described using the same compartmental models","authors":"Nils Hoem ,&nbsp;Stephen Harris ,&nbsp;Grace Scott ,&nbsp;Petter-Arnt Hals","doi":"10.1016/j.plefa.2025.102671","DOIUrl":"10.1016/j.plefa.2025.102671","url":null,"abstract":"<div><div>To investigate the systemic kinetics of EPA and DHA across different lipid classes, male rats were administered [1–¹⁴C]-radiolabelled EPA and DHA as triglycerides (TAG), phosphatidylcholine (PC), or lyso-phosphatidylcholine (LPC) by gavage. LPC was also administered intravenously. Plasma and whole blood concentration-time profiles were recorded from 0 to 168 hours, while cumulative radioactivity in expired air, faeces, and urine was recorded for up to 336 hours.</div><div>Non-compartmental analysis and compartmental modelling demonstrated overall first-order radiotracer kinetics for both fatty acids, with comparable terminal half-lives. The primary difference was in maximum concentration (Cmax ((µg-eq/g)/(mg/kg)): DHA = 0.18± 0.089, EPA = 0.24± 0.103; P &lt; 0.0001). Between TAG and PC, only time to maximum concentration (Tmax (h)) differed (PC = 3.23 ± 0.94, TAG = 2.55 ± 0.77; P = 0.0004). LPC showed significant differences from TAG and PC in area under the curve (AUC0-inf), Cmax, Tmax, and total clearance (CL/F (mL/(kg h))). Cumulative radioactivity levels in expired air and faeces were consistent with blood and plasma kinetics.</div><div>As suggested by early-phase (0 to 48 hours) radioactivity accumulation, which deviated from first-order behaviour, TAG and PC, but not LPC, exhibited some faecal loss without systemic absorption.</div><div>The compartmental models developed performed equally well for radiolabelled EPA and DHA, regardless of whether administered as TAG, PC, or LPC. The model can be adapted to handle non-zero endogenous baselines and was successfully applied to non-radiolabelled EPA, docosapentaenoic acid (DPA), and DHA, quantified via LC-MS/MS. These models can be applied to both radioactive and stable isotopes and adapted to include organ-specific kinetics, as well as those of EPA, DPA, and DHA in other species, including humans.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"205 ","pages":"Article 102671"},"PeriodicalIF":3.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642243","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":"Trans 10, cis 12-conjugated linoleic acid alleviates vascular fibrosis in obese mice","authors":"Shuai Yu ,&nbsp;Yu Rao ,&nbsp;Jiaqi Lu,&nbsp;Jiarun Li,&nbsp;Baozhu Wang,&nbsp;Kemian Gou","doi":"10.1016/j.plefa.2025.102669","DOIUrl":"10.1016/j.plefa.2025.102669","url":null,"abstract":"<div><div>Controlling food intake and improving fat distribution are crucial for preventing and treating cardiovascular disease. Trans-10, cis-12 conjugated linoleic acid (t10c12-CLA) can inhibit fat deposition and facilitate bodyweight reduction, suggesting its potential to safeguard against cardiovascular disease. The transgenic (tg) mice, which inserted Pai expression cassette into the Rosa26 locus, can produce endogenous t10c12-CLA. In the present study, we used tg mice to evaluate whether the long-term existence of t10c12-CLA has a protective effect on the vascular fibrosis phenotype. The male wild-type (wt) and tg mice were marked as wt+chow, tg+chow, wt+HFD and tg+HFD groups with 24 weeks feeding the chow diet or high-fat diet (HFD). Compared with wt+chow and tg+chow mice, wt+HFD mice showed a significant (<em>P</em> &lt; 0.05) increase in bodyweight and circulating lipid levels. The arterial blood vessels of wt+HFD mice displayed obvious lipid streaks and disorganization of collagen fibers. While compared with wt+HFD mice, tg+HFD mice showed a significant (<em>P</em> &lt; 0.05) decrease in body weight and circulating lipid levels. The arterial blood vessels of tg+HFD mice displayed slight foam cells, predicting that t10c12-CLA can alleviates vascular fibrosis degree caused by HFD. The RNA and protein expression of proinflammatory factors in arterial blood vessels of tg+HFD mice were significantly (<em>P</em> &lt; 0.05) decreased than those of wt+HFD mice. In conclusion, long-term existence of t10c12-CLA can improve lipid metabolism and circulating lipid levels and inhibit vascular inflammation and vascular fibrosis degree in obese mice, thereby preventing the further development of cardiovascular disease.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"204 ","pages":"Article 102669"},"PeriodicalIF":3.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480177","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}

{"title":"Plasma saturated fatty acids are inversely associated with lean mass and strength in adults: NHANES 2011–2012","authors":"Heitor O. Santos,&nbsp;Rafaela Nehme,&nbsp;Larissa S. Limirio,&nbsp;Maria Eduarda de F. Mendonça,&nbsp;Flávia M.S. de Branco,&nbsp;Erick P. de Oliveira","doi":"10.1016/j.plefa.2025.102667","DOIUrl":"10.1016/j.plefa.2025.102667","url":null,"abstract":"<div><h3>Background &amp; aims</h3><div>Several studies have suggested that increased intake of saturated fatty acids (SFAs) may have a pro-inflammatory effect, potentially impacting muscle mass and strength. However, the relationship of plasma SFAs and their subtypes (which reflect dietary SFA intake) with muscle mass and strength remains poorly understood. This study aimed to evaluate the association of plasma SFAs with lean mass and handgrip strength in adults.</div></div><div><h3>Methods</h3><div>A cross-sectional study was conducted with 896 participants aged 20-59 years, selected from a subsample of the National Health and Nutrition Examination Survey (NHANES) 2011–2012. Total plasma SFAs and their subtypes were detected using gas chromatography-mass spectrometry. Lean mass was assessed using dual-energy X-ray absorptiometry, with evaluations of both total lean mass and appendicular lean mass. Muscle strength was measured using a handgrip dynamometer, with combined grip strength calculated by summing the highest values from each hand. Linear regression analysis was conducted to examine the association between plasma SFAs, lean mass, and handgrip strength, adjusting for potential confounders.</div></div><div><h3>Results</h3><div>Total lean mass was negatively associated with total plasma SFAs and several of their subtypes such as plasma levels of stearic acid, palmitic acid, arachidic acid, tricosanoic acid, lignoceric acid, and docosanoic acid. Similarly, appendicular lean mass was negatively associated with total plasma SFAs, as well as with several specific subtypes, including palmitic acid, stearic acid, margaric acid, pentadecanoic acid, and myristic acid. Handgrip strength also demonstrated a negative association with total plasma SFAs, including specific subtypes such as lauric acid, palmitic acid, capric acid, margaric acid, pentadecanoic acid, and myristic acid.</div></div><div><h3>Conclusion</h3><div>Total plasma SFAs and several of their subtypes are inversely associated with lean mass and muscle strength in adults.</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"204 ","pages":"Article 102667"},"PeriodicalIF":3.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143387452","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}

{"title":"Association between the COX-2 rs689466 polymorphism and antipsychotic treatment: Impact on HDL cholesterol changes in clozapine-treated psychosis patients","authors":"Sergej Nadalin ,&nbsp;Ivan Ljoka ,&nbsp;Aleksandar Savić ,&nbsp;Ante Silić ,&nbsp;Vjekoslav Peitl ,&nbsp;Dalibor Karlović ,&nbsp;Maja Vilibić ,&nbsp;Lena Zatković ,&nbsp;Alena Buretić-Tomljanović","doi":"10.1016/j.plefa.2025.102665","DOIUrl":"10.1016/j.plefa.2025.102665","url":null,"abstract":"<div><div>Several studies have shown antipsychotic effects of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib as an add-on treatment to antipsychotic treatment. The functional rs689466 (A/G) polymorphism in the gene encoding COX-2 (also known as the prostaglandin-endoperoxide synthase 2 gene) has been correlated with schizophrenia risk and the niacin skin flush response among chronic patients under antipsychotic treatment. Here, we investigated whether this polymorphism was associated with antipsychotic treatment in a group of total psychosis patients (<em>N</em> = 186), as well as a subgroup of patients treated with clozapine (<em>N</em> = 74). Antipsychotic-naïve first-episode patients and non-adherent chronic psychosis patients were genotyped by polymerase chain reaction/restriction fragment length polymorphism analysis. At baseline and after 8 weeks of treatment with various antipsychotic medications, we assessed the patients’ Positive and Negative Syndrome Scale (PANSS) scores, factors, and metabolic syndrome-related parameters, including fasting plasma lipid and glucose levels and body mass index. In the total patient group, the COX-2 polymorphism was not associated with PANSS psychopathology scores or metabolic parameters. However, in the subgroup of patients treated with clozapine, the COX-2 polymorphism was associated with changes in plasma HDL cholesterol. Specifically, compared to patients homozygous for the A allele, the subgroup of patients treated with clozapine and positive for the G allele (i.e., GG or AG genotype) exhibited significantly higher increases in HDL cholesterol levels. The COX-2 polymorphism had a moderate effect size but made a relatively weak contribution to variations in the HDL cholesterol level (∼9.6 %).</div></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"204 ","pages":"Article 102665"},"PeriodicalIF":3.0,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143144376","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}