Biochimica et biophysica acta. Molecular and cell biology of lipids最新文献

{"title":"Changes in bile acid composition are correlated with reduced intestinal cholesterol uptake in intestine-specific WASH-deficient mice","authors":"Andries Heida ,&nbsp;Theo van Dijk ,&nbsp;Marieke Smit ,&nbsp;Martijn Koehorst ,&nbsp;Mirjam Koster ,&nbsp;Niels Kloosterhuis ,&nbsp;Rick Havinga ,&nbsp;Vincent W. Bloks ,&nbsp;Justina C. Wolters ,&nbsp;Alain de Bruin ,&nbsp;Jan Albert Kuivenhoven ,&nbsp;Jan Freark de Boer ,&nbsp;Folkert Kuipers ,&nbsp;Bart van de Sluis","doi":"10.1016/j.bbalip.2023.159445","DOIUrl":"10.1016/j.bbalip.2023.159445","url":null,"abstract":"<div><p>The Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) complex is a pentameric protein complex localized at endosomes, where it facilitates the transport of numerous receptors from endosomes toward the plasma membrane. Recent studies have shown that the WASH complex plays an essential role in cholesterol and glucose homeostasis in humans and mice. To investigate the physiological importance of intestinal WASH, we ablated the WASH component WASHC1 specifically in murine enterocytes. Male and female intestine-specific WASHC1-deficient mice (<em>Washc1</em>^IKO) were challenged with either a standard chow diet or a high-cholesterol (1.25 %) diet (HCD). <em>Washc1</em>^IKO mice fed a standard diet did not present any apparent phenotype, but when fed an HCD, their hepatic cholesterol levels were ~ 50 % lower compared to those observed in control mice. The intestinal cholesterol absorption was almost 2-fold decreased in <em>Washc1</em>^IKO mice, which translated into increased fecal neutral sterol loss. The intestinal expression of cholesterogenic genes, such as <em>Hmgcs1</em>, <em>Hmgcr</em>, and <em>Ldlr</em>, was significantly higher in <em>Washc1</em>^IKO mice than in control mice and correlated with increased whole-body de novo cholesterol synthesis, likely to compensate for impaired intestinal cholesterol absorption. Unexpectedly, the ratio of biliary 12α−/non-12α-hydroxylated bile acids (BAs) was decreased in <em>Washc1</em>^IKO mice and reversing this reduced ratio by feeding the mice with the HCD supplemented with 0.5 % (<em>w</em>/w) sodium cholate normalized the improvement of hepatic cholesterol levels in <em>Washc1</em>^IKO mice. Our data indicate that the intestinal WASH complex plays an important role in intestinal cholesterol absorption, likely by modulating biliary BA composition.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1388198123001695/pdfft?md5=85fb9a3ec7f964341f8d00bd741080ae&pid=1-s2.0-S1388198123001695-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138569898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic oxylipin profiles in mouse models of Wilson disease: New insights into early hepatic manifestations","authors":"Tagreed A. Mazi ,&nbsp;Noreene M. Shibata ,&nbsp;Gaurav V. Sarode ,&nbsp;Valentina Medici","doi":"10.1016/j.bbalip.2023.159446","DOIUrl":"10.1016/j.bbalip.2023.159446","url":null,"abstract":"<div><p>Hepatic inflammation is commonly identified in Wilson disease (WD), a genetic disease of hepatic and brain copper accumulation. Copper accumulation is associated with increased oxidative stress and reactive oxygen species generation which may result in non-enzymatic oxidation of membrane-bound polyunsaturated fatty acids (PUFA). PUFA can be oxidized enzymatically via lipoxygenases (LOX), cyclooxygenases (COX), and cytochrome P450 monooxygenases (CYP). Products of PUFA oxidation are collectively known as oxylipins (OXL) and are bioactive lipids that modulate hepatic inflammation. We examined hepatic OXL profiles at early stages of WD in two mouse models, the toxic milk mouse from The Jackson Laboratory (tx-j) and the <em>Atp7b</em> knockout on a C57Bl/6 background (<em>Atp7b</em>^−/−B6). Targeted lipidomic analysis performed by ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry showed that in both tx-j and <em>Atp7b</em>^−/−B6 mice, hepatic OXL profiles were altered with higher thromboxane and prostaglandins levels. The levels of oxidative stress marker, 9-HETE were increased more markedly in tx-j mice. However, both genotypes showed upregulated transcript levels of many genes related to oxidative stress and inflammation. Both genotypes showed higher prostaglandins, thromboxin along with higher PUFA-derived alcohols, diols, and ketones with altered epoxides; the expression of <em>Alox5</em> was upregulated and many CYP-related genes were dysregulated. Pathway analyses show dysregulation in arachidonic acid and linoleic acid metabolism characterizes mice with WD. Our findings indicate alterations in hepatic PUFA metabolism in early-stage WD and suggest the upregulation of both, non-enzymatic ROS-dependent and enzymatic PUFA oxidation, which could have implications for hepatic manifestations in WD and represent potential targets for future therapies.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2023-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1388198123001701/pdfft?md5=6c8ea604dc4bc9bb5a06e2e63f5c1d61&pid=1-s2.0-S1388198123001701-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138569897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ceramide regulation of autophagy: A biophysical approach","authors":"Yaiza R. Varela,&nbsp;Marina N. Iriondo,&nbsp;Félix M. Goñi,&nbsp;Alicia Alonso,&nbsp;L. Ruth Montes","doi":"10.1016/j.bbalip.2023.159444","DOIUrl":"10.1016/j.bbalip.2023.159444","url":null,"abstract":"<div><p>Specific membrane lipids play unique roles in (macro)autophagy. Those include phosphatidylethanolamine, to which LC3/GABARAP autophagy proteins become covalently bound in the process, or cardiolipin, an important effector in mitochondrial autophagy (or mitophagy). Ceramide (Cer), or N-acyl sphingosine, is one of the simplest sphingolipids, known as a stress signal in the apoptotic pathway. Moreover, Cer is increasingly being recognized as an autophagy activator, although its mechanism of action is unclear. In the present review, the proposed Cer roles in autophagy are summarized, together with some biophysical properties of Cer in membranes. Possible pathways for Cer activation of autophagy are discussed, including specific protein binding of the lipid, and Cer-dependent perturbation of bilayer properties. Cer generation of lateral inhomogeneities (domain formation) is given special attention. Recent biophysical results, including fluorescence and atomic force microscopy data, show Cer-promoted enhanced binding of LC3/GABARAP to lipid bilayers. These observations could be interpreted in terms of the putative formation of Cer-rich nanodomains.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1388198123001683/pdfft?md5=7e64144e53370668f533480c94d9ca62&pid=1-s2.0-S1388198123001683-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138497726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction of ROMK2 channel with lipid kinases DGKE and AGK: Potential channel activation by localized anionic lipid synthesis","authors":"Milena Krajewska ,&nbsp;Mariusz Możajew ,&nbsp;Sławomir Filipek ,&nbsp;Piotr Koprowski","doi":"10.1016/j.bbalip.2023.159443","DOIUrl":"10.1016/j.bbalip.2023.159443","url":null,"abstract":"<div><p><span>In this study, we utilized enzyme-catalyzed proximity labeling with the engineered promiscuous biotin<span> ligase<span> Turbo-ID to identify the proxisome of the ROMK2 channel. This channel resides in various cellular membrane compartments of the cell including the plasma membrane, endoplasmic reticulum and mitochondria. Within mitochondria, ROMK2 has been suggested as a pore-forming subunit of mitochondrial ATP-regulated potassium channel (mitoK</span></span></span>_ATP<span><span>). We found that ROMK2 proxisome in addition to previously known protein partners included two lipid<span><span> kinases: acylglycerol kinase (AGK) and diacylglycerol kinase ε (DGKE), which are localized in mitochondria and the endoplasmic reticulum, respectively. Through co-immunoprecipitation, we confirmed that these two kinases are present in complexes with ROMK2 channels. Additionally, we found that the products of AGK and DGKE, </span>lysophosphatidic acid (LPA) and </span></span>phosphatidic acid<span><span><span> (PA), stimulated the activity of ROMK2 channels in artificial lipid bilayers. Our </span>molecular docking studies revealed the presence of acidic lipid binding sites in the ROMK2 channel, similar to those previously identified in Kir2 channels. Based on these findings, we propose a model wherein localized </span>lipid synthesis, mediated by channel-bound lipid kinases, contributes to the regulation of ROMK2 activity within distinct intracellular compartments, such as mitochondria and the endoplasmic reticulum.</span></span></p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2023-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138497727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AMP deaminase: A crucial regulator in nitrogen stress and lipid metabolism in Mucor circinelloides","authors":"Shaoqi Li ,&nbsp;Junhuan Yang ,&nbsp;Hassan Mohamed ,&nbsp;Xiuwen Wang ,&nbsp;Wenyue Shi ,&nbsp;Futing Xue ,&nbsp;Sergio López-García ,&nbsp;Qing Liu ,&nbsp;Yuanda Song","doi":"10.1016/j.bbalip.2023.159434","DOIUrl":"10.1016/j.bbalip.2023.159434","url":null,"abstract":"<div><p><span>Lipid biosynthesis is a significant metabolic response to nitrogen starvation in oleaginous fungi. The oleaginous fungus </span><span><em>Mucor circinelloides</em></span><span><span> copes with nitrogen stress by degrading AMP through AMP deaminase (AMPD). However, the mechanism of AMPD in regulating lipogenesis remains largely unclear. To elucidate the mechanism of AMPD in </span>lipid synthesis in this </span><em>M. circinelloides</em>, we identified two genes (<em>ampd1</em> and <em>ampd2</em>) encoding AMPD and constructed an <em>ampd</em> double knockout mutant. The engineered <em>M. circinelloides</em><span><span><span> strain elevated cell growth and lipid accumulation, as well as the content of </span>oleic acid (OA) and gamma-linolenic acid (GLA). In addition to the expected increase in transcription levels of genes associated with lipid and </span>TAG<span><span><span> synthesis, we observed suppression of lipid degradation<span> and reduced amino acid biosynthesis. This suggested that the deletion of AMPD genes induces the redirection of carbon towards lipid synthesis pathways. Moreover, the pathways related to </span></span>nitrogen metabolism, including </span>nitrogen assimilation<span> and purine metabolism<span> (especially energy level), were also affected in order to maintain homeostasis. Further analysis discovered that the transcription factors (TFs) related to lipid accumulation were also regulated. This study provides new insights into lipid biosynthesis in </span></span></span></span><em>M. circinelloides</em>, indicating that the trigger for lipid accumulation is not entirely AMPD-dependent and suggest that there may be additional mechanisms involved in the initiation of lipogenesis.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2023-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deficiency of Brummer lipase disturbs lipid mobilization and locomotion, and impairs reproduction due to defects in the eggshell ultrastructure in the insect vector Rhodnius prolixus","authors":"Daniela Saar Arêdes ,&nbsp;Thamara Rios ,&nbsp;Luiz Fernando Carvalho-Kelly ,&nbsp;Valdir Braz ,&nbsp;Luciana O. Araripe ,&nbsp;Rafaela V. Bruno ,&nbsp;José Roberto Meyer-Fernandes ,&nbsp;Isabela Ramos ,&nbsp;Katia C. Gondim","doi":"10.1016/j.bbalip.2023.159442","DOIUrl":"10.1016/j.bbalip.2023.159442","url":null,"abstract":"<div><p><span><em>Rhodnius prolixus</em></span><span> is a hematophagous insect, which feeds on large and infrequent blood meals, and is a vector of trypanosomatids<span><span><span> that cause Chagas disease. After feeding, lipids derived from blood meal are stored in the fat body as </span>triacylglycerol, which is recruited under conditions of energy demand by </span>lipolysis<span>, where the first step is catalyzed by the Brummer lipase (Bmm), whose orthologue in mammals is the adipose triglyceride lipase (ATGL). Here, we investigated the roles of Bmm in adult </span></span></span><em>Rhodnius prolixus</em> under starvation, and after feeding. Its gene (<em>RhoprBmm</em>) was expressed in all the analyzed insect organs, and its transcript levels in the fat body were not altered by nutritional status. RNAi-mediated knockdown of <em>RhoprBmm</em><span> caused triacylglycerol retention in the fat body during starvation, resulting in larger lipid droplets and lower ATP levels compared to control females. The silenced females showed decreased flight capacity and locomotor activity. When </span><em>RhoprBmm</em><span><span> knockdown occurred before the blood meal and the insects were fed, the females laid fewer eggs, which collapsed and showed low hatching rates. Their hemolymph had reduced diacylglycerol<span> content and vitellogenin concentration. The </span></span>chorion<span> (eggshell) of their eggs had no difference in hydrocarbon amounts or in dityrosine crosslinking levels compared to control eggs. However, it showed ultrastructural defects. These results demonstrated that Bmm activity is important not only to guarantee lipid mobilization to maintain energy homeostasis during starvation, but also for the production of viable eggs after a blood meal, by somehow contributing to the right formation of the egg chorion.</span></span></p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138476678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Palmitic acid activates NLRP3 inflammasome through NF-κB and AMPK-mitophagy-ROS pathways to induce IL-1β production in large yellow croaker (Larimichthys crocea)","authors":"Xueshan Li ,&nbsp;Kangsen Mai ,&nbsp;Qinghui Ai","doi":"10.1016/j.bbalip.2023.159428","DOIUrl":"10.1016/j.bbalip.2023.159428","url":null,"abstract":"<div><p><span>Studies on marine fish showed that vegetable oils substituted for excessive fish oil increased interleukin-1β (IL-1β) production. However, whether the nucleotide-binding oligomerization<span> domain, leucine-rich repeat-containing family, pyrin domain-containing-3 (NLRP3) inflammasome has a substantial role in fatty acid-induced IL-1β production in fish remains unclear. The associated specific mechanism is also unknown. In this study, </span></span><em>nlrp3</em>, <em>caspase-1</em> and apoptosis-associated speck-like protein containing a CARD (<em>asc</em><span>) were successfully cloned, and NLRP3<span> inflammasome consisted of NLRP3, caspase-1 and ASC in large yellow croaker. Primary hepatocytes of fish incubated with palmitic acid (PA) exhibited the highest expression of pro-inflammatory genes (</span></span><em>il-1β</em> and <em>tnfα</em>) and NLRP3 inflammasome related genes (<em>nlrp3</em>, <em>caspase-1</em> and <em>asc</em>), caspase-1 activity and IL-1β production among different treatments. Furthermore, PA-induced NLRP3 inflammasome activation was confirmed to require two signals: the first signal was that PA promoted the NF-κB (P65) protein into the nucleus, and NF-κB increased NLRP3 promoter activity and <em>nlrp3</em><span> transcription. The second signal was that PA inhibited AMPK phosphorylation and decreased mitophagy by inhibiting the expression of PINK and parkin proteins, thereby damaging the mitochondria that could not be effectively cleared. Mitochondrial damage generated excessive amounts of reactive oxygen species, which activated the NLRP3 inflammasome and then induced caspase-1 activity and IL-1β production. Therefore, excessive dietary PA activated NLRP3 inflammasome through NF-κB and AMPK-mitophagy-ROS pathways to induce IL-1β production, thereby leading to inflammation in fish.</span></p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2023-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138457599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Taste receptor type 1 member 3 regulates Western diet-induced male infertility","authors":"Hobin Seong ,&nbsp;Jae Won Song ,&nbsp;Keon-Hee Lee ,&nbsp;Goo Jang ,&nbsp;Dong-Mi Shin ,&nbsp;Woo-Jeong Shon","doi":"10.1016/j.bbalip.2023.159433","DOIUrl":"10.1016/j.bbalip.2023.159433","url":null,"abstract":"<div><p><span>Western diet (WD), characterized by a high intake of fats and sugary drinks, is a risk factor for male reproductive impairment. However, the molecular mechanisms underlying this remain unclear. Taste receptor type 1 member 3 (TAS1R3), activated by ligands of WD, is highly expressed in extra-oral tissues, particularly in the testes. Here, we investigated to determine the effects of WD intake on male reproduction and whether TAS1R3 mediates WD-induced impairment in male reproduction. Male C57BL/6 J wild-type (WT) and </span><em>Tas1r3</em><span> knockout (KO) mice were fed either a normal diet and plain water (ND) or a 60 % high-fat-diet and 30 % (w/v) sucrose water (WD) for 18 weeks (n = 7–9/group). Long-term WD consumption significantly impaired sperm count, motility and testicular morphology in WT mice with marked </span><em>Tas1r3</em> overexpression, whereas <em>Tas1r3</em><span><span> KO mice were protected from WD-induced reproductive impairment. Testicular transcriptome analysis revealed downregulated AMP-activated protein kinase (AMPK) signaling and significantly elevated AMPK-targeted </span>nuclear receptor 4A1 (</span><em>Nr4a1</em>) expression in WD-fed <em>Tas1r3</em><span> KO mice. In vitro studies further validated that </span><em>Tas1r3</em><span> knockdown in Leydig cells prevented the suppression of </span><em>Nr4a1</em> and downstream steroidogenic genes (<em>Star</em>, <span><em>Cyp11a1</em></span>, <em>Cyp17a1</em>, and <em>Hsd3b1</em><span>) caused by high glucose, fructose, and palmitic acid levels, and maintained the levels of testosterone. Additionally, we analyzed the public human dataset to assess the clinical implications of our findings and confirmed a significant association between TAS1R3 and male-infertility-related diseases. Our findings suggest that TAS1R3 regulates WD-induced male reproductive impairment via the AMPK/NR4A1 signaling and can be a novel therapeutic target for male infertility.</span></p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138440272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eicosanoid profiles in an arthritis model: Effects of a soluble epoxide hydrolase inhibitor","authors":"Carlos Antonio Trindade-da-Silva ,&nbsp;Jun Yang ,&nbsp;Flavia Fonseca ,&nbsp;Hoang Pham ,&nbsp;Marcelo Henrique Napimoga ,&nbsp;Henrique Ballassini Abdalla ,&nbsp;Geanpaolo Aver ,&nbsp;Márcio José Alves De Oliveira ,&nbsp;Bruce D. Hammock ,&nbsp;Juliana Trindade Clemente-Napimoga","doi":"10.1016/j.bbalip.2023.159432","DOIUrl":"10.1016/j.bbalip.2023.159432","url":null,"abstract":"<div><p>Rheumatoid arthritis is a common systemic inflammatory autoimmune disease characterized by damage to joints, inflammation and pain. It is driven by an increase of inflammatory cytokines<span><span><span> and lipids<span> mediators such as prostaglandins. Epoxides of polyunsaturated fatty acids (PUFAs) are lipid chemical mediators in a group of regulatory compounds termed </span></span>eicosanoids<span>. These epoxy fatty acids (EpFA) have resolutive functions but are rapidly metabolized by the soluble epoxide hydrolase<span> enzyme<span> (sEH) into the corresponding diols. The pharmacological inhibition of sEH stabilizes EpFA from hydrolysis, improving their half-lives and biological effects. These anti-inflammatory EpFA, are analgesic in neuropathic and inflammatory pain conditions. Nonetheless, inhibition of sEH on arthritis and the resulting effects on eicosanoids profiles are little explored despite the physiological importance. In this study, we investigated the effect of sEH inhibition on collagen-induced arthritis (CIA) and its impact on the plasma eicosanoid profile. We measured the eicosanoid metabolites by LC–MS/MS-based </span></span></span></span>lipidomic<span> analysis. The treatment with a sEH inhibitor significantly modulated 11 out of 69 eicosanoids, including increased epoxides 12(13)-EpODE, 12(13)-EpOME, 13-oxo-ODE, 15-HEPE, 20-COOH-LTB4 and decreases several diols 15,6-DiHODE, 12,13-DiHOME, 14,15-DiHETrE, 5,6-DiHETrE and 16,17-DiHDPE. Overall the inhibition of sEH in the rheumatoid arthritis model enhanced epoxides generally considered anti-inflammatory or resolutive mediators and decreased several diols with inflammatory features. These findings support the hypothesis that inhibiting the sEH increases systemic EpFA levels, advancing the understanding of the impact of these lipid mediators as therapeutical targets.</span></span></p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2023-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138175409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of ERA protein in enhancing glyceroglycolipid synthesis and phosphate starvation tolerance in Synechococcus elongatus PCC 7942","authors":"Junhao Li,&nbsp;Rui Wang,&nbsp;Yuhong Liu,&nbsp;Xiaoling Miao","doi":"10.1016/j.bbalip.2023.159431","DOIUrl":"10.1016/j.bbalip.2023.159431","url":null,"abstract":"<div><p><span>Glyceroglycolipids are the primary thylakoid membrane<span> lipids in cyanobacteria. Their diverse bioactivities have led to extensive utilization in the biomedical industry. In this study, we elucidated the role of ERA (</span></span><em>E. coli</em> Ras-like protein) in augmenting glyceroglycolipid synthesis and bolstering stress resilience in <span><em>Synechococcus elongatus</em></span> PCC 7942 during phosphate starvation. Notably, the ERA overexpression strain (ERA OE) outperformed the wild-type (WT) strain under phosphate-starved conditions, displaying an average 13.9 % increase in biomass over WT during the entire growth period, peaking at 0.185 g L⁻¹<span> of dry cell weight on day 6. Lipidomic<span> analysis using UHPLC-MS/MS techniques revealed that ERA OE exhibited a higher total glyceroglycolipid content compared to WT under phosphate starvation, representing a 7.95 % increase over WT and constituting a maximum of 5.07 % of dry cell weight on day 6. Transcriptomic analysis identified a significant up-regulation of the </span></span><em>gldA</em> gene (encoding glycerol dehydrogenase) involved in glycerolipid metabolism due to overexpression of <em>ERA</em> during phosphate starvation. These findings suggest a potential mechanism by which ERA regulates glyceroglycolipid synthesis through the up-regulation of GldA, thereby enhancing phosphate starvation tolerance in <em>S. elongatus</em><span><span> PCC 7942. Furthermore, lipidomic analysis revealed that ERA facilitated the production of glyceroglycolipid molecules containing C16:1 and C18:1 fatty acids. Additionally, ERA redirected lipid flux and promoted glyceroglycolipid accumulation while attenuating </span>triacylglycerol production under phosphate starvation. This study represents the first demonstration of pivotal role of ERA in enhancing glyceroglycolipid synthesis and phosphate starvation tolerance in cyanobacteria, offering new insights into the effective utilization of glyceroglycolipids in various applications.</span></p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2023-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136396016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}