Prostaglandins, leukotrienes, and essential fatty acids最新文献

{"title":"Gallein but not fluorescein enhances the PGD2-stimulated synthesis of osteoprotegerin and interleukin-6 in osteoblasts","authors":"","doi":"10.1016/j.plefa.2024.102639","DOIUrl":"10.1016/j.plefa.2024.102639","url":null,"abstract":"<div><p>Gallein, a small molecule related to fluorescein, is established as an inhibitor of Gβγ subunits to inhibit G protein (Gs) signaling. This agent is providing a potential therapeutic strategy to ameliorate organ dysfunctions especially involved in inflammation, however; the effects on bone metabolism have not yet been clarified. Prostaglandins (PGs) play important roles as autacoids including osteoblasts, and <span>d</span>-type prostanoid (DP) receptor, a member of G protein-coupled receptor specific to PGD₂, is expressed on osteoblasts. We previously reported that prostaglandin D₂ (PGD₂) induces the syntheses of osteoprotegerin (OPG) and interleukin-6 (IL-6), essential factors in bone remodelling process, and p38 mitogen-activated protein kinase (MAPK), c-<em>Jun</em> N-terminal kinase (JNK), and p44/p42 MAPK are involved in the signal transduction of PGD₂ in osteoblast-like MC3T3-E1 cells. Thus, we investigated in this study that the effect and the underlying mechanism of gallein, an inhibitor Gβɤ subunits, on the syntheses of OPG and IL-6 induced by PGD₂ in these cells. The cultured cells were treated with gallein or fluorescein, a structurally related compound inactive to Gβɤ subunits, and subsequently stimulated with PGD₂. Not fluorescein but gallein amplified the PGD₂-stimulated releases of OPG and IL-6. Gallein enhanced the PGD₂-upregulated mRNA expression levels of OPG and IL-6. Regarding the signaling mechanism, gallein did not affect the PGD₂-induced phosphorylation of p38 MAPK, JNK, or p42 MAPK. In conclusion, gallein upregulates the PGD₂-stimulated syntheses of OPG and IL-6 by the specific effect to inhibit Gβγ subunits in osteoblasts, but the effect is not exerted at the upstream of p38 MAPK, JNK, or p44/p42 MAPK activation.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142172596","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":"Omega-3 fatty acids mitigate skin damage caused by ultraviolet-B radiation","authors":"","doi":"10.1016/j.plefa.2024.102641","DOIUrl":"10.1016/j.plefa.2024.102641","url":null,"abstract":"<div><p>Mice fed a diet containing an adequate amount of ω-3 fatty acids (ω-3 Adq) or a deficient diet (ω-3 Def) were irradiated with ultraviolet-B (UV-B) and were measured daily changes in transepidermal water loss (TEWL). TEWL was significantly increased in ω-3 Def mice with repeated UV-B irradiation, but this increase was significantly reduced in ω-3 Adq mice. The epidermal layers revealed thickening of the spinous and basal layers induced by UV-B irradiation in both groups. Moreover, the ω-3 Def mice had a disturbed epidermal structure and a coarser stratum corneum. And the granule cell layer is significantly reduced, and abnormal layer formation (parakeratosis) occurred in the stratum corneum. These results suggest that continuous UV-B irradiation promotes epidermal turnover and leads to epidermal thickening, but ω-3 fatty acids protect the body from UV-B-induced stress.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0952327824000358/pdfft?md5=c3429b485f7e0c2196629fd7f048d66d&pid=1-s2.0-S0952327824000358-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142238087","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":"Unsaturated fatty acids, omega-3 index and hospitalization in MISC","authors":"Elisabetta Di Profio ,&nbsp;Patrizia Risé ,&nbsp;Lara Orlandi ,&nbsp;Elena Zoia ,&nbsp;Christian Pinna ,&nbsp;Angelo Sala ,&nbsp;Gianvincenzo Zuccotti ,&nbsp;Elvira Verduci","doi":"10.1016/j.plefa.2024.102627","DOIUrl":"10.1016/j.plefa.2024.102627","url":null,"abstract":"<div><p>The growing interest in Omega-3 fatty acids as diagnostic markers or new therapeutic approaches also for COVID-19 disease, led us to investigate the presence of potential correlations between Omega-3 fatty acids’ levels in whole blood and days of hospitalization or admission to the paediatric intensive care unit (PICU) in 51 children with MIS-C diagnosis following SARS-CoV-2 infection. A statistically significant negative correlation was observed between days of hospitalization and docosapentaenoic acid (22:5n-3,DPA), docosahexaenoic acid (DHA) and total Omega-3 FA levels. Dividing the study group into quartiles according to Omega-3-Index (O3I), no statistically significant difference was observed with respect to the PICU admission rate. In contrast, the number of days of hospitalization in Q4 (O3I ≥ 2.51 %) was different from the number observed in groups Q1-3 (O3I &lt; 2.51 %), with subjects showing higher O3I needing shorter hospitalizations than the subjects with lower O3I. According to previous study investigating O3I in adults affected by Sars-cov-2 we explored the levels of this nutrients in children with MIS-C. Our exploratory study shows that high DPA, DHA and O3I levels could be effective in reducing the length of hospitalization.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141536293","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":"Expression of dihomo-γ-linolenic acid and FADS1/2 and ELOVL2/5 in term rabbit placentas","authors":"M. Kyogashima ,&nbsp;K. Kamijima ,&nbsp;N. Takai ,&nbsp;T. Nakajima ,&nbsp;T. Mikuma ,&nbsp;H. Komamura ,&nbsp;K. Asai ,&nbsp;M. Ishihara ,&nbsp;E. Sugiyama ,&nbsp;N. Tanaka","doi":"10.1016/j.plefa.2024.102629","DOIUrl":"10.1016/j.plefa.2024.102629","url":null,"abstract":"<div><p>Long-chain polyunsaturated fatty acids (LCPUFAs) are essential for both fetal and placental development. We characterized the FA composition and gene expression levels of FA-metabolizing enzymes in rabbit placentas. Total FA compositions from term rabbit placentas (<em>n</em> = 7), livers, and plasma (both <em>n</em> = 4) were examined: among LCPUFAs with more than three double bonds, dihomo-γ-linolenic acid (DGLA) was the most abundant (11.4 ± 0.69 %, mean ± SE), while arachidonic acid was the second-most rich component (6.90 ± 0.56 %). DGLA was barely detectable (&lt;1 %) in livers and plasma from term rabbits, which was significantly lower than in placentas (both <em>p</em> &lt; 0.0001). Compared with the liver, transcript levels of the LCPUFA-metabolizing enzymes <em>FADS2</em> and <em>ELOVL5</em> were 7- and 4.5-fold higher in placentas (both <em>p</em> &lt; 0.05), but levels of <em>FADS1</em> and <em>ELOVL2</em> were significantly lower (both <em>p</em> &lt; 0.01). Our results suggest a placenta-specific enzyme expression pattern and LCPUFA profile in term rabbits, which may support a healthy pregnancy.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141604708","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":"Omega-3 supplementation changes the physical properties of leukocytes but not erythrocytes in healthy individuals: An exploratory trial","authors":"","doi":"10.1016/j.plefa.2024.102636","DOIUrl":"10.1016/j.plefa.2024.102636","url":null,"abstract":"<div><p>n3-PUFA impact health in several ways, including cardiovascular protection and anti-inflammatory effects, but the underlying mechanisms are not fully understood. In this exploratory study involving 31 healthy subjects, we aimed to investigate the effects of 12 weeks of fish-oil supplementation (1500 mg EPA+DHA/day) on the physical properties of multiple blood cell types. We used deformability cytometry (DC) for all cell types and Laser-assisted Optical Rotational Red Cell Analysis (Lorrca) to assess red blood cell (RBC) deformability. We also investigated the correlation between changes in the physical properties of blood cells and changes in the Omega-3 Index (O3I), defined as the relative content of EPA+DHA in RBCs. Following supplementation, the mean±SD O3I increased from 5.3 %±1.5 % to 8.3 %±1.4 % (<em>p</em> &lt; 0.001). No significant changes in RBC properties were found by both techniques. However, by DC we observed a consistent pattern of physical changes in lymphocytes, neutrophils and monocytes. Among these were significant increases in metrics correlated with the cells’ deformability resulting in less stiff cells. The results suggest that leukocytes become softer and have an increased ability to deform under induced short-term physical stress such as hydrodynamic force in the circulation. These changes could impact immune function since softer leukocytes can potentially circulate more easily and could facilitate a more rapid response to systemic inflammation or infection. In conclusion, fish-oil supplementation modulates some physical properties of leukocyte-subfractions, potentially enhancing their biological function. Further studies are warranted to explore the impact of n3-PUFA on blood cell biology, particularly in disease states associated with leukocyte dysregulation.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0952327824000309/pdfft?md5=9a213a7932b43f9f753997531eab28d8&pid=1-s2.0-S0952327824000309-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142002442","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":"Beneficial effects of dietary omega 3 polyunsaturated fatty acids on offspring brain development in gestational diabetes mellitus","authors":"","doi":"10.1016/j.plefa.2024.102632","DOIUrl":"10.1016/j.plefa.2024.102632","url":null,"abstract":"<div><p>Various mechanisms through which maternal diet influences offspring brain development in gestational diabetes mellitus (GDM) remains unclear. We speculate that prenatal omega 3 fatty acids will improve the levels of brain neurotrophins and vascular endothelial growth factor (VEGF), an angiogenic factor leading to improved cognitive performance in the offspring. GDM was induced in Wistar rats using streptozotocin. They were assigned to either control, GDM or GDM+O (GDM + omega-3 fatty acid supplementation). The offspring were followed till 3 mo of age and cognitive assessment was undertaken. Data analysis was carried out using one-way ANOVA followed by LSD test. GDM induction increased (<em>p</em> &lt; 0.01) dam glucose levels and lowered brain derived neurotrophic factor (BDNF) levels (<em>p</em> = 0.056) in the offspring at birth. At 3 months, GDM group showed significantly lower levels of neurotrophic tyrosine kinase receptor-2 (NTRK-2) and VEGF, lower mRNA levels of NTRK-2 and cAMP response element-binding protein (CREB) (<em>P</em> &lt; 0.05 for all) as compared to control. The GDM offspring had a higher escape latency (<em>p</em> &lt; 0.01), made lesser % correct choices and more errors (<em>p</em> &lt; 0.05 for both). Prenatal supplementation with omega 3 polyunsaturated fatty acids was beneficial since it ameliorated some of the adverse effects of GDM.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141639205","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":"Resolvin D1 suppresses macrophage senescence and splenic fibrosis in aged mice","authors":"","doi":"10.1016/j.plefa.2024.102634","DOIUrl":"10.1016/j.plefa.2024.102634","url":null,"abstract":"<div><p>Aging is associated with systemic, non-resolving inflammation and the accumulation of senescent cells. The resolution of inflammation (or inflammation-resolution) is in part mediated by the balance between specialized pro-resolving mediators (SPMs) and pro-inflammatory leukotrienes (LTs). Aged mice (<em>i.e.</em> 2 years of age) exhibit a significant decrease in the SPM:LT ratio in specific organs including the spleen, which suggests that this organ may exhibit heightened inflammation and may be particularly amenable to SPM therapy. Previous studies have shown that resolvin D1 (RvD1) is decreased in spleens of aged mice compared with young controls. Therefore, we asked whether treatment of RvD1 in aged mice would impact markers of cellular senescence in splenic macrophages, and downstream effects on splenic fibrosis, a hallmark of splenic aging. We found that in aged mice, both zymosan-elicited and splenic macrophages showed an increase in mRNA expression of inflammatory and eicosanoid biosynthesis genes and a dysregulation of genes involved in the cell cycle. Injections with RvD1 reversed these changes. Importantly, RvD1 also decreased splenic fibrosis, a hallmark of splenic aging. Our findings suggest that RvD1 treatment may limit several features of aging, including senescence and fibrosis in spleens from aged mice.</p><p>Summary</p><p>Aging is associated with systemic, low grade, non-resolving inflammation. The resolution of inflammation is in part mediated by the balance between specialized pro-resolving mediators (SPMs) and pro-inflammatory lipid mediators, like leukotrienes (LTs). A hallmark of aging is the accumulation of senescent cells that promote low grade inflammation by secreting pro-inflammatory cytokines and lipid mediators. Splenic macrophages contribute to systemic aging, and spleens of aged mice demonstrate decreased levels of the SPM called resolvin D1 (RvD1). Whether addition of RvD1 is protective in spleens of aged mice is unknown and is focus of this study. RvD1 treatment to aged mice led to decreased mRNA expression of markers of cellular senescence and inflammation in splenic macrophages compared with age-matched vehicle controls. Moreover, RvD1 decreased splenic fibrosis, which occurs due to persistent low-grade inflammation in aging. Promoting inflammation resolution with RvD1 thus limits macrophage senescence, pro-inflammatory signals and established splenic fibrosis in aging.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0952327824000280/pdfft?md5=ca1753c7b731d8b4498be533e5a9a91e&pid=1-s2.0-S0952327824000280-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142011783","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":"Regular moderate physical activity potentially accelerates and strengthens both the pro-inflammatory and pro-resolving lipid mediator response after acute exercise stress","authors":"","doi":"10.1016/j.plefa.2024.102642","DOIUrl":"10.1016/j.plefa.2024.102642","url":null,"abstract":"<div><p>The PUFA-derived lipid mediator response shifts from pro-inflammatory to inflammation resolution over time and may be modified by regular moderate exercise. This pre-post-test study aimed to compare the expression of PTGES2 (COX2) and ALOX15 in leucocytes and the plasma 5- and 15-HETE, 18-HEPE and 17-HDHA responses after unaccustomed resistance exercise between 18–35-year-old male recreational runners (n = 18) and less-active controls (n = 15). One repetition maximum (1RM) was determined for squats, 45° leg presses and leg extensions. Subsequently three sets of 8–10 repetitions were performed at 80 % 1RM and blood collected over 72 hours. <em>PTGES2</em> and <em>ALOX15</em> expression changed over time in runners (<em>P</em> = 0.016, <em>P</em> = 0.007) but not controls (<em>P = 0.631, P = 0.539</em>). 5- and 15-HETE changed over time in runners (<em>P &lt; 0.001, P = 0.022</em>), but not controls (<em>P = 0.457, P = 0.985</em>). 18-HEPE changed in runners and controls (<em>P &lt; 0.001, P = 0.024</em>), 17-HDHA changed borderline in runners (<em>P = 0.076</em>). In conclusion, pro-inflammatory and inflammation-resolving lipid mediators may respond sooner and more robust in recreational runners than less-active controls after strenuous resistance exercise.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S095232782400036X/pdfft?md5=3cc9915dc54b4b1126fc97e1cdb713a2&pid=1-s2.0-S095232782400036X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142098724","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":"Inhibition of 15-prostaglandin dehydrogenase attenuates acetaminophen-induced liver injury via suppression of apoptosis in liver endothelial cells","authors":"","doi":"10.1016/j.plefa.2024.102640","DOIUrl":"10.1016/j.plefa.2024.102640","url":null,"abstract":"<div><p>Hepatic microvascular disruption caused by injury to liver sinusoidal endothelial cells (LSECs) is an aggravating factor for drug-induced liver injury (DILI). It is suggested that prostaglandin E₂ (PGE₂) may be able to attenuate LSEC injury. However, it is also known that 15-keto PGE₂, a metabolite of PGE₂ produced by 15-prostaglandin dehydrogenase (15-PGDH) that is not a ligand of PGE₂ receptors, suppresses inflammatory acute liver injury as a ligand of peroxisome proliferator-activated receptor γ. In this study, we aimed to understand whether 15-PGDH activity is essential for preventing DILI by suppressing hepatic microvascular disruption in a mouse model of acetaminophen (APAP)-induced liver injury. To inhibit 15-PGDH activity prior to APAP-induced LSEC injury, we administered the 15-PGDH inhibitor, SW033291, 1 h before and 3 h after APAP treatment. We observed that LSEC injury preceded hepatocellular injury in APAP administered mice. Hepatic endogenous PGE₂ levels did not increase up till the initiation of LSEC injury but rather increased after hepatocellular injury. Moreover, hepatic 15-PGDH activity was downregulated in APAP-induced liver injury. The inhibition of 15-PGDH attenuated LSEC injury and subsequently hepatic injury by inhibiting apoptosis in APAP administered mice. Our <em>in vitro</em> studies also suggested that PGE₂ inhibited APAP-induced apoptosis via the EP4/PI3K pathway in endothelial cells. Therefore, a decrease in 15-PGDH activity would be beneficial for preventing APAP-induced liver injury by attenuating LSEC injury.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142098726","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":"9-HODE and 9-HOTrE alter mitochondrial metabolism, increase triglycerides, and perturb fatty acid uptake and synthesis associated gene expression in HepG2 cells","authors":"","doi":"10.1016/j.plefa.2024.102635","DOIUrl":"10.1016/j.plefa.2024.102635","url":null,"abstract":"<div><p>Non-Alcoholic Fatty Liver Disease (NAFLD) prevalence is rising and can lead to detrimental health outcomes such as Non-Alcoholic Steatohepatitis (NASH), cirrhosis, and cancer. Recent studies have indicated that Cytochrome P450 2B6 (CYP2B6) is an anti-obesity CYP in humans and mice. Cyp2b-null mice are diet-induced obese, and human CYP2B6-transgenic (hCYP2B6-Tg) mice reverse the obesity or diabetes progression, but with increased liver triglyceride accumulation in association with an increase of several oxylipins. Notably, 9-hydroxyoctadecadienoic acid (9-HODE) produced from linoleic acid (LA, 18:2, ω-6) is the most prominent of these and 9-hydroxyoctadecatrienoic acid (9-HOTrE) from alpha-linolenic acid (ALA, 18:3, ω-3) is the most preferentially produced when controlling for substrate concentrations in vitro. Transactivation assays indicate that 9-HODE and 9-HOTrE activate PPARα and PPARγ. In Seahorse assays performed in HepG2 cells, 9-HOTrE increased spare respiratory capacity, slightly decreased palmitate metabolism, and increased non-glycolytic acidification in a manner consistent with slightly increased glutamine utilization; however, 9-HODE exhibited no effect on metabolism. Both compounds increased triglyceride and pyruvate concentrations, most strongly by 9-HOTrE, consistent with increased spare respiratory capacity. qPCR analysis revealed several perturbations in fatty acid uptake and metabolism gene expression. 9-HODE increased expression of CD36, FASN, PPARγ, and FoxA2 that are involved in lipid uptake and production. 9-HOTrE decreased ANGPTL4 expression and increased FASN expression consistent with increased fatty acid uptake, fatty acid production, and AMPK activation. Our findings support the hypothesis that 9-HODE and 9-HOTrE promote steatosis, but through different mechanisms as 9-HODE is directly involved in fatty acid uptake and synthesis; 9-HOTrE weakly inhibits mitochondrial fatty acid metabolism while increasing glutamine use.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141978377","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}