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

{"title":"The function of sphingolipids in membrane trafficking and cell signaling in plants, in comparison with yeast and animal cells","authors":"Louise Fougère,&nbsp;Sebastien Mongrand,&nbsp;Yohann Boutté","doi":"10.1016/j.bbalip.2024.159463","DOIUrl":"10.1016/j.bbalip.2024.159463","url":null,"abstract":"<div><p>Sphingolipids are essential membrane components involved in a wide range of cellular, developmental and signaling processes. Sphingolipids are so essential that knock-out mutation often leads to lethality. In recent years, conditional or weak allele mutants as well as the broadening of the pharmacological catalog allowed to decipher sphingolipid function more precisely in a less invasive way. This review intends to provide a discussion and point of view on the function of sphingolipids with a main focus on endomembrane trafficking, Golgi-mediated protein sorting, cell polarity, cell-to-cell communication and cell signaling at the plasma membrane. While our main angle is the plant field research, we will constantly refer to and compare with the advances made in the yeast and animal field. In this review, we will emphasize the role of sphingolipids not only as a membrane component, but also as a key player at a center of homeostatic regulatory networks involving direct or indirect interaction with other lipids, proteins and ion fluxes.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 3","pages":"Article 159463"},"PeriodicalIF":4.8,"publicationDate":"2024-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139569841","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":"Silencing ANGPTL8 reduces mouse preadipocyte differentiation and insulin signaling","authors":"Anindya Ghosh ,&nbsp;Yat Hei Leung ,&nbsp;Jeffrey Yu ,&nbsp;Robert Sladek ,&nbsp;Isabelle Chénier ,&nbsp;Abel K. Oppong ,&nbsp;Marie-Line Peyot ,&nbsp;S.R. Murthy Madiraju ,&nbsp;Irina Al-Khairi ,&nbsp;Thangavel Alphonse Thanaraj ,&nbsp;Jehad Abubaker ,&nbsp;Fahd Al-Mulla ,&nbsp;Marc Prentki ,&nbsp;Mohamed Abu-Farha","doi":"10.1016/j.bbalip.2024.159461","DOIUrl":"10.1016/j.bbalip.2024.159461","url":null,"abstract":"<div><p>ANGPTL8, expressed mainly in the liver and adipose tissue, regulates the activity of lipoprotein lipase (LPL) present in the extracellular space and triglyceride (TG) metabolism through its interaction with ANGPTL3 and ANGPTL4. Whether intracellular ANGPTL8 can also exert effects in tissues where it is expressed is uncertain. ANGPTL8 expression was low in preadipocytes and much increased during differentiation. To better understand the role of intracellular ANGPTL8 in adipocytes and assess whether it may play a role in adipocyte differentiation, we knocked down its expression in normal mouse subcutaneous preadipocytes. ANGPTL8 knockdown reduced adipocyte differentiation, cellular TG accumulation and also isoproterenol-stimulated lipolysis at day 7 of differentiation. RNA-Seq analysis of ANGPTL8 siRNA or control siRNA transfected SC preadipocytes on days 0, 2, 4 and 7 of differentiation showed that ANGPTL8 knockdown impeded the early (day 2) expression of adipogenic and insulin signaling genes, PPARγ, as well as genes related to extracellular matrix and NF-κB signaling. Insulin mediated Akt phosphorylation was reduced at an early stage during adipocyte differentiation. This study based on normal primary cells shows that ANGPTL8 has intracellular actions in addition to effects in the extracellular space, like modulating LPL activity. Preadipocyte ANGPTL8 expression modulates their differentiation possibly via changes in insulin signaling gene expression.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 3","pages":"Article 159461"},"PeriodicalIF":4.8,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1388198124000118/pdfft?md5=04f9f18b32a10231e88df16f39b8f53f&pid=1-s2.0-S1388198124000118-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139560317","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":"Protective effect of oleic acid against very long-chain fatty acid-induced apoptosis in peroxisome-deficient CHO cells","authors":"Hanif Ali,&nbsp;Mone Yamanishi,&nbsp;Keigo Sunagawa,&nbsp;Mizuki Kumon,&nbsp;Rumana Yesmin Hasi,&nbsp;Mutsumi Aihara,&nbsp;Ryushi Kawakami,&nbsp;Tamotsu Tanaka","doi":"10.1016/j.bbalip.2024.159452","DOIUrl":"10.1016/j.bbalip.2024.159452","url":null,"abstract":"<div><p>Very long-chain fatty acids (VLCFAs) are degraded exclusively in peroxisomes<span>, as evidenced by the accumulation of VLCFAs in patients with certain peroxisomal disorders. Although accumulation of VLCFAs is considered to be associated with health issues, including neuronal degeneration, the mechanisms underlying VLCFAs-induced tissue degeneration remain unclear. Here, we report the toxic effect of VLCFA and protective effect of C18: 1 FA in peroxisome-deficient CHO cells. We examined the cytotoxicity of saturated and monounsaturated VLCFAs with chain-length at C20–C26, and found that longer and saturated VLCFA showed potent cytotoxicity at lower accumulation levels. Furthermore, the extent of VLCFA-induced toxicity was found to be associated with a decrease in cellular C18:1 FA levels. Notably, supplementation with C18:1 FA effectively rescued the cells from VLCFA-induced apoptosis without reducing the cellular VLCFAs levels, implying that peroxisome-deficient cells can survive in the presence of accumulated VLCFA, as long as the cells keep sufficient levels of cellular C18:1 FA. These results suggest a therapeutic potential of C18:1 FA in peroxisome disease and may provide new insights into the pharmacological effect of Lorenzo's oil, a 4:1 mixture of C18:1 and C22:1 FA.</span></p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 3","pages":"Article 159452"},"PeriodicalIF":4.8,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139496113","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":"SIRT1-dependent PGC-1α deacetylation by SRT1720 rescues progression of atherosclerosis by enhancing mitochondrial function","authors":"Jin Young Sung ,&nbsp;Seul Gi Kim ,&nbsp;Young Jin Kang ,&nbsp;So-Young Park ,&nbsp;Hyoung Chul Choi","doi":"10.1016/j.bbalip.2024.159453","DOIUrl":"10.1016/j.bbalip.2024.159453","url":null,"abstract":"<div><p><span><span>Vascular smooth muscle cell (VSMC) senescence promotes atherosclerosis via lipid-mediated mitochondrial dysfunction and oxidative stress. However, the mechanisms of mitochondrial dysfunction and VSMC senescence in atherosclerosis have not been established. Here, we investigated the mechanisms whereby </span>signaling pathways<span><span> regulated by SRT1720 enhance or regulate mitochondrial functions in atherosclerotic VSMCs to suppress atherosclerosis. Initially, we examined the effect of SRT1720 on oleic acid<span> (OA)-induced atherosclerosis. Atherosclerotic VSMCs exhibited elevated expressions of BODIPY and ADRP (adipose differentiation-related protein) and associated intracellular lipid droplet markers. In addition, the expression of collagen I was upregulated by OA, while the expressions of </span></span>elastin<span> and α-SMA were downregulated. mtDNA copy numbers, an ATP detection assay, transmission electron microscopy<span> (TEM) imaging of mitochondria, mitochondria membrane potentials (assessed using JC-1 probe), and levels of mitochondrial </span></span></span></span>oxidative phosphorylation<span><span> (OXPHOS) were used to examine the effects of SRT1720 on OA-induced mitochondrial dysfunction. SRT1720 reduced mtDNA damage and accelerated mitochondria repair in VSMCs with OA-induced mitochondria dysfunction. In addition, mitochondrial reactive oxygen species (mtROS) levels were downregulated by SRT1720 in OA-treated VSMCs. Importantly, SRT1720 significantly increased SIRT1 and PGC-1α expression levels, but VSMCs senescence, inflammatory response, and atherosclerosis phenotypes were not recovered by treating cells with EX527 and SR-18292 before SRT1720. Mechanistically, the upregulations of SIRT1 and PGC-1α </span>deacetylation by SRT1720 restored mitochondrial function, and consequently suppressed VSMC senescence and atherosclerosis-associated proteins and phenotypes.</span></p><p>Collectively, this study indicates that SRT1720 can attenuate OA-induced atherosclerosis associated with VSMC senescence and mitochondrial dysfunction via SIRT1-mediated deacetylation of the PGC-1α pathway.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 3","pages":"Article 159453"},"PeriodicalIF":4.8,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139496106","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":"The role of areA in lipid accumulation in high lipid-producing fungus Mucor circinelloides WJ11","authors":"Haisu Hu ,&nbsp;Pengcheng Li ,&nbsp;Shaoqi Li ,&nbsp;Xiuwen Wang ,&nbsp;Hassan Mohamed ,&nbsp;Sergio López-García ,&nbsp;Qing Liu ,&nbsp;Victoriano Garre ,&nbsp;Yuanda Song","doi":"10.1016/j.bbalip.2023.159450","DOIUrl":"10.1016/j.bbalip.2023.159450","url":null,"abstract":"<div><p>In the oleaginous fungus <span><em>Mucor circinelloides</em></span><span><span>, lipid accumulation is regulated by </span>nitrogen metabolism, which is regulated by the </span><em>areA</em><span> gene, a member of the GATA zinc finger transporter family and a major regulator for nitrogen metabolism. However, the role of </span><em>areA</em><span> in lipid accumulation in this fungus has not been reported. In order to explore the regulatory effect of </span><em>areA</em> gene on nitrogen metabolism and lipid accumulation in <em>M. circinelloides</em>, we constructed <em>areA</em><span> gene knockout and overexpression strains. Then, the recombinant strains were cultured and their biochemical indexes were measured. Simultaneously, transcriptomic studies on the recombinant strains were conducted to infer the regulatory mechanism of </span><em>areA</em>. The results showed that the <em>areA</em> knockout strain accumulated more lipid, which is 42 % higher than the control. While the <em>areA</em><span> overexpressing strain obtained the higher biomass accumulation (23 g/L) and used up the nitrogen source in the medium earlier than the control strain and knockout strain. Transcriptome data analysis showed that </span><em>nr</em> and <em>nit-6</em> genes related to nitrogen metabolism were up-regulated. And the expression levels of key genes <em>acc</em> and <em>aclY</em> were higher in the <em>areA</em><span> knockout strain than others, which was positively correlated with the increased lipid accumulation. In addition, in knockout strains, protein catabolism tended to provide substrates for the lipid production, and the expression levels of the related genes were also higher than others. These results indicated that the </span><em>areA</em> gene not only controls the transcription level of genes related to nitrogen metabolism but also affects lipid accumulation.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 2","pages":"Article 159450"},"PeriodicalIF":4.8,"publicationDate":"2024-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139373757","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":"Sex modulates the diet-induced changes to the plasma lipidome in a rat model of cardiorespiratory fitness","authors":"Johanna Y. Fleischman ,&nbsp;James L. Casey ,&nbsp;Jennifer L. Meijer ,&nbsp;Mary K. Treutelaar ,&nbsp;Thekkelnaycke M. Rajendiran ,&nbsp;Tanu Soni ,&nbsp;Charles R. Evans ,&nbsp;Charles F. Burant","doi":"10.1016/j.bbalip.2024.159451","DOIUrl":"10.1016/j.bbalip.2024.159451","url":null,"abstract":"<div><h3>Objective</h3><p>Individuals with higher intrinsic cardiorespiratory fitness (CRF) experience decreased rates of cardiometabolic disease and mortality, and high CRF is associated with increased utilization of fatty acids (FAs) for energy. Studies suggest a complex relationship between CRF, diet, and sex with health outcomes, but this interaction is understudied. We hypothesized that FA utilization differences by fitness and sex could be detected in the plasma metabolome when rats or humans were fed a high carbohydrate (HC) or high fat (HF) diet.</p></div><div><h3>Methods</h3><p>Male and female rats selectively bred for low (LCR) and high (HCR) CRF were fed a chow diet or a sucrose-free HF (45 % fat) or HC (10 % fat) diet. Plasma samples were collected at days 0, 3, and 14. Human plasma data was collected from male and female participants who were randomized into a HC or HF diet for 21 days. Samples were analyzed using liquid chromatography-mass spectrometry and regression statistics were used to quantify the effect of diet, CRF, and sex on the lipidome.</p></div><div><h3>Results</h3><p>In rats, the baseline lipidome is more significantly influenced by sex than by CRF, especially as elevated diglycerides, triglycerides, phosphatidylcholines, and lysophosphatidylcholines in males. A dynamic response to diet was observed 3 days after diet, but after 14 days of either diet, the lipidome was modulated by sex with a larger effect size than by diet. Data from the human study also suggests a sex-dependent response to diet with opposite directionality of affect compared to rats, highlighting species-dependent responses to dietary intervention.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 3","pages":"Article 159451"},"PeriodicalIF":4.8,"publicationDate":"2024-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139373793","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":"Sensing and regulation of long-chain polyunsaturated fatty acids pool in marine mollusks: Characterization of UBXD8 from the razor clam Sinonovacula constricta","authors":"Zhaoshou Ran ,&nbsp;Haixuan Xie ,&nbsp;Xuxu Tian ,&nbsp;Fei Kong ,&nbsp;Kai Liao ,&nbsp;Xiaojun Yan ,&nbsp;Jilin Xu","doi":"10.1016/j.bbalip.2023.159448","DOIUrl":"10.1016/j.bbalip.2023.159448","url":null,"abstract":"<div><p>The razor clam <em>Sinonovacula constricta</em><span> is known for its richness in long-chain polyunsaturated fatty acids (LC-PUFA, C ≥ 20). Previously, we demonstrated that it possesses a complete LC-PUFA biosynthetic pathway. However, the mechanisms by which it senses the LC-PUFA pool to regulate their biosynthesis remain unclear. Here, we presented the LC-PUFA sensor UBXD8 as a critical molecule in this intriguing process. The </span><em>S. constricta</em> UBXD8 (<em>Sc</em><span>UBXD8) shared all characteristic features of its mammalian counterpart and exhibited high mRNA levels in digestive tissues, suggesting its functional role in this bivalve species. By purification of </span><em>Sc</em>UBXD8 protein <em>in vitro</em><span>, we discovered its ability to sense unsaturated fatty acids (UFA, C ≥ 14) but not saturated ones, as evidenced by polymerization detection. Furthermore, the intensity of </span><em>Sc</em>UBXD8 polymerization increased progressively with longer acyl chain lengths, greater unsaturation degrees, and higher UFA concentrations. Exceptionally, for those located at the same node in LC-PUFA biosynthetic pathway, <em>Sc</em>UBXD8 displayed a stronger sensitivity to n-6 UFA compared to n-3 UFA. These results suggested a critical role for <em>Sc</em><span>UBXD8 in balancing fatty acids composition and ratio of n-6/n-3 UFA in </span><em>S. constricta</em>. Moreover, the UAS domain was confirmed essential for <em>Sc</em>UBXD8 polymerization. Through knockdown of <em>Sc</em>Ubxd8 gene <em>in vivo</em>, there were significant shifts in expression patterns of genes related to LC-PUFA biosynthesis, concurrently influencing fatty acids compositions. These results suggested that <em>Sc</em>UBXD8 likely plays a regulatory role in LC-PUFA biosynthesis, possibly through the INSIG-SREBP pathway. Collectively, this study proposed that <em>S. constricta</em><span> might maintain LC-PUFA homeostasis through UBXD8 to regulate their biosynthesis.</span></p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 2","pages":"Article 159448"},"PeriodicalIF":4.8,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139092846","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":"Discovery of novel diagnostic biomarkers for Sjögren-Larsson syndrome by untargeted lipidomics","authors":"Frédéric M. Vaz ,&nbsp;Pippa Staps ,&nbsp;Jan Bert van Klinken ,&nbsp;Henk van Lenthe ,&nbsp;Martin Vervaart ,&nbsp;Ronald J.A. Wanders ,&nbsp;Mia L. Pras-Raves ,&nbsp;Michel van Weeghel ,&nbsp;Gajja S. Salomons ,&nbsp;Sacha Ferdinandusse ,&nbsp;Ron A. Wevers ,&nbsp;Michèl A.A.P. Willemsen","doi":"10.1016/j.bbalip.2023.159447","DOIUrl":"10.1016/j.bbalip.2023.159447","url":null,"abstract":"<div><h3>Aim</h3><p>Sjögren-Larsson syndrome (SLS) is a rare neurometabolic disorder that mainly affects brain, eye and skin and is caused by deficiency of fatty aldehyde dehydrogenase. Our recent finding of a profoundly disturbed brain tissue lipidome in SLS prompted us to search for similar biomarkers in plasma as no functional test in blood is available for SLS.</p></div><div><h3>Methods and results</h3><p>We performed plasma lipidomics and used a newly developed bioinformatics tool to mine the untargeted part of the SLS plasma and brain lipidome to search for SLS biomarkers. Plasma lipidomics showed disturbed ether lipid metabolism in known lipid classes. Untargeted lipidomics of both plasma and brain (white and grey matter) uncovered two new endogenous lipid classes highly elevated in SLS. The first biomarker group were alkylphosphocholines/ethanolamines containing different lengths of alkyl-chains where some alkylphosphocholines were &gt; 600-fold elevated in SLS plasma. The second group of biomarkers were a set of 5 features of unknown structure. Fragmentation studies suggested that they contain ubiquinol and phosphocholine and one feature was also found as a glucuronide conjugate in plasma. The plasma features were highly distinctive for SLS with levels &gt;100–1000-fold the level in controls, if present at all. We speculate on the origin of the alkylphosphocholines/ethanolamines and the nature of the ubiquinol-containing metabolites.</p></div><div><h3>Conclusions</h3><p>The metabolites identified in this study represent novel endogenous lipid classes thus far unknown in humans. They represent the first plasma metabolite SLS-biomarkers and may also yield more insight into SLS pathophysiology.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 2","pages":"Article 159447"},"PeriodicalIF":4.8,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1388198123001713/pdfft?md5=28cc58c350aaf496cf5c9ec6eb1b54e0&pid=1-s2.0-S1388198123001713-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139092817","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":"Human ApoC3 overexpression aggravates hyperlipidemia but mitigates diet-induced coronary atherosclerotic disease in SR-BI and LDL receptor double knockout mice","authors":"Jiawei Liao ,&nbsp;Yuhui Wang ,&nbsp;Yao Wang ,&nbsp;Jinjin Zhang ,&nbsp;Feng Wu ,&nbsp;George Liu ,&nbsp;Wei Huang ,&nbsp;Ying Zhang","doi":"10.1016/j.bbalip.2023.159449","DOIUrl":"10.1016/j.bbalip.2023.159449","url":null,"abstract":"","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 3","pages":"Article 159449"},"PeriodicalIF":4.8,"publicationDate":"2023-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139064526","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":"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":"1869 2","pages":"Article 159445"},"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}