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

{"title":"Architecture and function of yeast phosphatidate phosphatase Pah1 domains/regions","authors":"Geordan J. Stukey,&nbsp;Gil-Soo Han,&nbsp;George M. Carman","doi":"10.1016/j.bbalip.2024.159547","DOIUrl":"10.1016/j.bbalip.2024.159547","url":null,"abstract":"<div><p>Phosphatidate (PA) phosphatase, which catalyzes the Mg²⁺-dependent dephosphorylation of PA to produce diacylglycerol, provides a direct precursor for the synthesis of the storage lipid triacylglycerol and the membrane phospholipids phosphatidylcholine and phosphatidylethanolamine. The enzyme controlling the key phospholipid PA also plays a crucial role in diverse aspects of lipid metabolism and cell physiology. PA phosphatase is a peripheral membrane enzyme that is composed of multiple domains/regions required for its catalytic function and subcellular localization. In this review, we discuss the domains/regions of PA phosphatase from the yeast <em>Saccharomyces cerevisiae</em> with reference to the homologous enzyme from mammalian cells.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 8","pages":"Article 159547"},"PeriodicalIF":3.9,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1388198124000970/pdfft?md5=c0bad1fd3e0858c472094011213bebc1&pid=1-s2.0-S1388198124000970-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892786","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":"Tissue-specific sex-dependent difference in the metabolism of fatty acid esters of hydroxy fatty acids","authors":"Martin Riecan ,&nbsp;Veronika Domanska ,&nbsp;Cristina Lupu ,&nbsp;Maulin Patel ,&nbsp;Michaela Vondrackova ,&nbsp;Martin Rossmeisl ,&nbsp;Alan Saghatelian ,&nbsp;Florea Lupu ,&nbsp;Ondrej Kuda","doi":"10.1016/j.bbalip.2024.159543","DOIUrl":"10.1016/j.bbalip.2024.159543","url":null,"abstract":"<div><p>Fatty acid esters of hydroxy fatty acids (FAHFAs) are endogenous bioactive lipids known for their anti-inflammatory and anti-diabetic properties. Despite their therapeutic potential, little is known about the sex-specific variations in FAHFA metabolism. This study investigated the role of sex and Androgen Dependent TFPI Regulating Protein (ADTRP), a FAHFA hydrolase. Additionally, tissue-specific differences in FAHFA levels, focusing on the perigonadal white adipose tissue (pgWAT), subcutaneous white adipose tissue (scWAT), brown adipose tissue (BAT), plasma, and liver, were evaluated using metabolomics and lipidomics. We found that female mice exhibited higher FAHFA levels in pgWAT, scWAT, and BAT compared to males. FAHFA levels were inversely related to testosterone and <em>Adtrp</em> mRNA, which showed significantly lower expression in females compared with males in pgWAT and scWAT. However, no significant differences between the sexes were observed in plasma and liver FAHFA levels. <em>Adtrp</em> deletion had minimal impact on both sexes' metabolome and lipidome of pgWAT. However, we discovered higher endogenous levels of triacylglycerol estolides containing FAHFAs, a FAHFA metabolic reservoir, in the pgWAT of female mice. These findings suggest that sex-dependent differences in FAHFA levels occur primarily in specific WAT depots and may modulate local insulin sensitivity in adipocytes, and the role of ADTRP is limited to adipose depots. However, further investigations are warranted to fully comprehend the underlying mechanisms and implications of sex-dependent regulation of human FAHFA metabolism.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 8","pages":"Article 159543"},"PeriodicalIF":3.9,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1388198124000933/pdfft?md5=bac19cab735d4893ee0e604d66d75410&pid=1-s2.0-S1388198124000933-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888385","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":"Targeted and untargeted lipidomics with integration of liver dynamics and microbiome after dietary reversal of obesogenic diet targeting inflammation-resolution signaling in aging mice","authors":"Gunjan Upadhyay ,&nbsp;Siddabasave Gowda B. Gowda ,&nbsp;Sidharth P. Mishra ,&nbsp;Lipsa Rani Nath ,&nbsp;Adewale James ,&nbsp;Alisha Kulkarni ,&nbsp;Yuktee Srikant ,&nbsp;Rohitram Upendram ,&nbsp;MathanKumar Marimuthu ,&nbsp;Shu-Ping Hui ,&nbsp;Shalini Jain ,&nbsp;Kain Vasundhara ,&nbsp;Hariom Yadav ,&nbsp;Ganesh V. Halade","doi":"10.1016/j.bbalip.2024.159542","DOIUrl":"10.1016/j.bbalip.2024.159542","url":null,"abstract":"<div><p>Obesity, a global epidemic linked to around 4 million deaths yearly, arises from lifestyle imbalances impacting inflammation-related conditions like non-alcoholic fatty liver disease and gut dysbiosis. But the long-term effects of inflammation caused by lifestyle-related dietary changes remain unexplained. In this study, we used young male C57Bl/6 mice which were fed either an obesogenic diet (OBD) or a control diet (CON) for six months. Later, a group of mice from the OBD group were intervened to the CON diet (OBD-R) for four months, while another OBD group remained on the OBD diet. The OBD induced distinct changes in gut microbial, notably elevating Firmicutes and Actinobacteria, while reducing Bacteroidetes and Tenericutes. OBD-R restored microbial abundance like CON. Analyzing liver, plasma, and fecal samples revealed OBD-induced alterations in various structural and bioactive lipids, which were normalized to CON in the OBD-R, showcasing lipid metabolism flexibility and adaptability to dietary shifts. OBD increased omega 6 fatty acid, Arachidonic Acid (AA) and decreased omega 3-derived lipid mediators in the OBD mimicking non-alcoholic fatty liver disease thus impacting inflammation-resolution pathways. OBD also induced hepatic inflammation via increasing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and proinflammatory markers CCR2, TNF-α, and IL-1β in liver. Transitioning from OBD to CON mitigated inflammatory gene expression and restored lipid and cholesterol networks. This study underscores the intricate interplay between lifestyle-driven dietary changes, gut microbiota, lipid metabolism, and liver health. Notably, it suggests that shift from an OBD (omega-6 enriched) to CON partially alleviates signs of chronic inflammation during aging. Understanding these microbial, lipidomic, and hepatic inflammatory dynamics reveals potential therapeutic avenues for metabolic disorders induced by diet, emphasizing the pivotal role of diet in sustaining metabolic health.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 8","pages":"Article 159542"},"PeriodicalIF":3.9,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888384","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":"Dissection of the synthesis of polyunsaturated fatty acids in nematodes and Collembola of the soil fauna","authors":"Ralph Menzel,&nbsp;Kevin Tobias,&nbsp;Tugce Fidan,&nbsp;Alexandra Rietz,&nbsp;Liliane Ruess","doi":"10.1016/j.bbalip.2024.159541","DOIUrl":"10.1016/j.bbalip.2024.159541","url":null,"abstract":"<div><p>It is becoming increasingly clear that not only unicellular, photoautotrophic eukaryotes, plants, and fungi, but also invertebrates are capable of synthesizing ω3 long-chain polyunsaturated fatty acids (LC-PUFA) <em>de novo</em>. However, the distribution of this anabolic capacity among different invertebrate groups and its implementation at the gene and protein level are often still unknown. This study investigated the PUFA pathways in common soil fauna, <em>i.e.</em> two nematode and two Collembola species. Of these, one species each (<em>Panagrellus redivivus</em>, <em>Folsomia candida</em>) was assumed to produce ω3 LC-PUFA <em>de novo</em>, while the others (<em>Acrobeloides bodenheimeri</em>, <em>Isotoma caerulea</em>) were supposed to be unable to do so. A highly labeled oleic acid (99 % ¹³C) was supplemented and the isotopic signal was used to trace its metabolic path. All species followed the main pathway of lipid biosynthesis. However, in <em>A. bodenheimeri</em> this terminated at arachidonic acid (ω6 PUFA), whereas the other three species continued the pathway to eicosapentaenoic acid (ω3 PUFA), including <em>I. caerulea</em>. For the nematode <em>P. redivivus</em> the identification and functional characterization of four new fatty acid desaturase (FAD) genes was performed. These genes encode the FAD activities Δ9, Δ6, and Δ5, respectively. Additionally, the Δ12 desaturase was analyzed, yet the observed activity of an ω3 FAD could not be attributed to a coding gene. In the Collembola <em>F. candida</em>, 11 potential first desaturases (Δ9) and 13 front-end desaturases (Δ6 or Δ5 FADs) have been found. Further sequence analysis indicates the presence of omega FADs, specifically Δ12, which are likely derived from Δ9 FADs.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 8","pages":"Article 159541"},"PeriodicalIF":3.9,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S138819812400091X/pdfft?md5=852b2d3d54b5dc7d19b88e2d92a23770&pid=1-s2.0-S138819812400091X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888386","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":"ABCA1 deficiency causes tissue-specific dysregulation of the SREBP2 pathway in mice","authors":"Yoshio Yamauchi ,&nbsp;Sumiko Abe-Dohmae ,&nbsp;Noriyuki Iwamoto ,&nbsp;Ryuichiro Sato ,&nbsp;Shinji Yokoyama","doi":"10.1016/j.bbalip.2024.159546","DOIUrl":"10.1016/j.bbalip.2024.159546","url":null,"abstract":"<div><p>ABCA1 plays an essential role in the formation of high-density lipoprotein (HDL), and its mutations cause Tangier disease (TD), a familial HDL deficiency. In addition to the disappearance of HDL, TD patients exhibit cholesterol deposition in peripheral tissues through a mechanism poorly understood, which may contribute to the development of premature atherosclerosis. We and others previously showed that ABCA1 deficiency causes hyperactivation of the SREBP2 pathway in vitro. Here, we show using <em>Abca1</em> knockout mice that ABCA1 deficiency leads to tissue-specific dysregulation of SREBP2 activity in a nutritional status-dependent manner, which may underlie the pathophysiology of TD.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 8","pages":"Article 159546"},"PeriodicalIF":3.9,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1388198124000969/pdfft?md5=16064d504a2ac0c2f886d60d538609a0&pid=1-s2.0-S1388198124000969-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874062","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":"A methionine-choline-deficient diet induces nonalcoholic steatohepatitis and alters the lipidome, metabolome, and gut microbiome profile in the C57BL/6J mouse","authors":"Jyoti Gautam ,&nbsp;Hobby Aggarwal,&nbsp;Deepika Kumari,&nbsp;Sonu Kumar Gupta,&nbsp;Yashwant Kumar,&nbsp;Madhu Dikshit","doi":"10.1016/j.bbalip.2024.159545","DOIUrl":"10.1016/j.bbalip.2024.159545","url":null,"abstract":"<div><p>The methionine-choline-deficient (MCD) diet-induced non-alcoholic steatohepatitis (NASH) in mice is a well-established model. Our study aims to elucidate the factors influencing liver pathology in the MCD mouse model by examining physiological, biochemical, and molecular changes using histology, molecular techniques, and OMICS approaches (lipidomics, metabolomics, and metagenomics). Male C57BL/6J mice were fed a standard chow diet, a methionine-choline-sufficient (MCS) diet, or an MCD diet for 10 weeks. The MCD diet resulted in reduced body weight and fat mass, along with decreased plasma triglyceride, cholesterol, glucose, and insulin levels. However, it notably induced steatosis, inflammation, and alterations in gene expression associated with lipogenesis, inflammation, fibrosis, and the synthesis of apolipoproteins, sphingolipids, ceramides, and carboxylesterases.</p><p>Lipid analysis revealed significant changes in plasma and tissues: most ceramide non-hydroxy-sphingosine lipids significantly decreased in the liver and plasma but increased in the adipose tissue of MCD diet-fed animals. Oxidized glycerophospholipids mostly increased in the liver but decreased in the adipose tissue of the MCD diet-fed group. The gut microbiome of the MCD diet-fed group showed an increase in Firmicutes and a decrease in Bacteroidetes and Actinobacteria. Metabolomic profiling demonstrated that the MCD diet significantly altered amino acid biosynthesis, metabolism, and nucleic acid metabolism pathways in plasma, liver, fecal, and cecal samples. LC-MS data indicated higher total plasma bile acid intensity and reduced fecal glycohyodeoxycholic acid intensity in the MCD diet group. This study demonstrates that although the MCD diet induces hepatic steatosis, the mechanisms underlying NASH in this model differ from those in human NASH pathology.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 8","pages":"Article 159545"},"PeriodicalIF":3.9,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874061","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 PAH1-encoded phosphatidate phosphatase of Yarrowia lipolytica differentially affects gene expression and lipid biosynthesis","authors":"Taylor Carmon,&nbsp;Na'Taja Hill,&nbsp;Venkateswara R. Sripathi,&nbsp;Zachary B. Gossett,&nbsp;Stylianos Fakas","doi":"10.1016/j.bbalip.2024.159544","DOIUrl":"10.1016/j.bbalip.2024.159544","url":null,"abstract":"<div><p><em>Yarrowia lipolytica</em> is a model oleaginous yeast with a strong capacity for lipid accumulation, yet its lipid metabolic pathways and regulatory mechanisms remain largely unexplored. The <em>PAH1</em>-encoded phosphatidate (PA) phosphatase governs lipid biosynthesis by its enzymatic activity and regulating the transcription of genes involved in phospholipid biosynthesis. In this work, we examined the effect of the loss of Pah1 (i.e., <em>pah1</em>Δ) on cell metabolism in cells growing in low- and high-glucose media. Multi-omics analyses revealed the global effect of the <em>pah1</em>Δ mutation on lipid and central carbon metabolism. Lipidomics analyses showed that the <em>pah1</em>Δ mutation caused a massive decrease in the masses of triacylglycerol (TAG) and diacylglycerol (DAG), and these effects were independent of glucose concentration in the media. Conversely, phospholipid levels declined in low-glucose media but increased in high-glucose media. The loss of Pah1 affected the expression of genes involved in key pathways of glucose metabolism, such as glycolysis, citric acid cycle, oxidative phosphorylation, and the pentose phosphate pathway, and these effects were more pronounced in high-glucose media. In lipid biosynthesis, the genes catalyzing phosphatidylcholine (PC) synthesis from phosphatidylethanolamine (PE) were upregulated within the CDP-DAG pathway. In contrast, PC synthesis through the Kennedy pathway was downregulated. The ethanolamine branch of the Kennedy pathway that synthesizes PE was also upregulated in <em>pah1</em>Δ. Interestingly, we noted a massive increase in the levels of lysophospholipids, consistent with the upregulation of genes involved in lipid turnover. Overall, this work identified novel regulatory roles of Pah1 in lipid biosynthesis and gene expression.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 8","pages":"Article 159544"},"PeriodicalIF":3.9,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141874063","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":"Lipidome of Acinetobacter baumannii antibiotic persister cells","authors":"Delphine Vergoz ,&nbsp;Annick Schaumann ,&nbsp;Isabelle Schmitz ,&nbsp;Carlos Afonso ,&nbsp;Emmanuelle Dé ,&nbsp;Corinne Loutelier-Bourhis ,&nbsp;Stéphane Alexandre","doi":"10.1016/j.bbalip.2024.159539","DOIUrl":"10.1016/j.bbalip.2024.159539","url":null,"abstract":"<div><p>Persister cells constitute a bacterial subpopulation able to survive to high concentrations of antibiotics. This phenotype is temporary and reversible, and thus could be involved in the recurrence of infections and emergence of antibiotic resistance. To better understand how persister cells survive to such high antibiotic concentration, we examined changes in their lipid composition. We thus compared the lipidome of <em>Acinetobacter baumannii</em> ATCC 19606^T persister cells formed under ciprofloxacin treatment with the lipidome of control cells grown without antibiotic. Using matrix assisted laser desorption ionisation-Fourier transform ion cyclotron resonance mass spectrometry, we observed a higher abundance of short chains and secondary chains without hydroxylation for lipid A in persister cells. Using liquid chromatography-tandem mass spectrometry, we found that persister cells produced particular phosphatidylglycerols, as LPAGPE and PAGPE, but also lipids with particular acyl chains containing additional hydroxyl group or uncommon di-unsaturation on C18 and C16 acyl chains. In order to determine the impact of these multiple lipidome modifications on membrane fluidity, fluorescence anisotropy assays were performed. They showed an increase of rigidity for the membrane of persister cells, inducing likely a decrease membrane permeability to protect cells during dormancy. Finally, we highlighted that <em>A. baumannii</em> persister cells also produced particular wax esters, composed of two fatty acids and a fatty diol. These uncommon storage lipids are key metabolites allowing a rapid bacterial regrow when antibiotic pressure disappears. These overall changes in persister lipidome may constitute new therapeutic targets to combat these particular dormant cells.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 7","pages":"Article 159539"},"PeriodicalIF":3.9,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787171","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":"Early activation of hepatic stellate cells induces rapid initiation of retinyl ester breakdown while maintaining lecithin:retinol acyltransferase (LRAT) activity","authors":"Maya W. Haaker,&nbsp;Vera Goossens,&nbsp;Nina A.N. Hoogland,&nbsp;Hidde van Doorne,&nbsp;Ziqiong Wang,&nbsp;Jeroen W.A. Jansen,&nbsp;Dora V. Kaloyanova,&nbsp;Chris H.A. van de Lest,&nbsp;Martin Houweling,&nbsp;A. Bas Vaandrager,&nbsp;J. Bernd Helms","doi":"10.1016/j.bbalip.2024.159540","DOIUrl":"10.1016/j.bbalip.2024.159540","url":null,"abstract":"<div><p>Lecithin:retinol acyltransferase (LRAT) is the main enzyme producing retinyl esters (REs) in quiescent hepatic stellate cells (HSCs). When cultured on stiff plastic culture plates, quiescent HSCs activate and lose their RE stores in a process similar to that in the liver following tissue damage, leading to fibrosis. Here we validated HSC cultures in soft gels to study RE metabolism in stable quiescent HSCs and investigated RE synthesis and breakdown in activating HSCs.</p><p>HSCs cultured in a soft gel maintained characteristics of quiescent HSCs, including the size, amount and composition of their characteristic large lipid droplets. Quiescent gel-cultured HSCs maintained high expression levels of <em>Lrat</em> and a RE storing phenotype with low levels of RE breakdown. Newly formed REs are highly enriched in retinyl palmitate (RP), similar to freshly isolated quiescent HSCs, which is associated with high LRAT activity. Comparison of these quiescent gel-cultured HSCs with activated plastic-cultured HSCs showed that although during early activation the total RE levels and RP-enrichment are reduced, levels of RE formation are maintained and mediated by LRAT. Loss of REs was caused by enhanced RE breakdown in activating HSCs. Upon prolonged culturing, activated HSCs have lost their LRAT activity and produce small amounts of REs by DGAT1. This study reveals unexpected dynamics in RE metabolism during early HSC activation, which might be important in liver disease as early stages are reversible. Soft gel cultures provide a promising model to study RE metabolism in quiescent HSCs, allowing detailed molecular investigations on the mechanisms for storage and release.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 7","pages":"Article 159540"},"PeriodicalIF":3.9,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1388198124000908/pdfft?md5=62a2e62b2ffedeed72c59c7bc898b487&pid=1-s2.0-S1388198124000908-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787233","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 stearoyl-CoA desaturase-1 deficiency induces fibrosis and hepatocellular carcinoma-related gene activation under a high carbohydrate low fat diet","authors":"Jayne-Norah Ntambi ,&nbsp;Mugagga Kalyesubula ,&nbsp;Dylan Cootway ,&nbsp;Sarah A. Lewis ,&nbsp;Yar Xin Phang ,&nbsp;Zhaojin Liu ,&nbsp;Lucas M. O'Neill ,&nbsp;Lucas Lefers ,&nbsp;Hailey Huff ,&nbsp;Jacqueline Rose Miller ,&nbsp;Veronica Pegkou Christofi ,&nbsp;Ethan Anderson ,&nbsp;Ahmed Aljohani ,&nbsp;Francis Mutebi ,&nbsp;Mainak Dutta ,&nbsp;Andrew Patterson ,&nbsp;James M. Ntambi","doi":"10.1016/j.bbalip.2024.159538","DOIUrl":"10.1016/j.bbalip.2024.159538","url":null,"abstract":"<div><p>Stearoyl-CoA desaturase-1 (SCD1) is a pivotal enzyme in lipogenesis, which catalyzes the synthesis of monounsaturated fatty acids (MUFA) from saturated fatty acids, whose ablation downregulates lipid synthesis, preventing steatosis and obesity. Yet deletion of SCD1 promotes hepatic inflammation and endoplasmic reticulum stress, raising the question of whether hepatic SCD1 deficiency promotes further liver damage, including fibrosis. To delineate whether SCD1 deficiency predisposes the liver to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC), we employed in vivo SCD1 deficient global and liver-specific mouse models fed a high carbohydrate low-fat diet and in vitro established AML12 mouse cells. The absence of liver SCD1 remarkably increased the saturation of liver lipid species, as indicated by lipidomic analysis, and led to hepatic fibrosis. Consistently, SCD1 deficiency promoted hepatic gene expression related to fibrosis, cirrhosis, and HCC. Deletion of SCD1 increased the circulating levels of Osteopontin, known to be increased in fibrosis, and alpha-fetoprotein, often used as an early marker and a prognostic marker for patients with HCC. De novo lipogenesis or dietary supplementation of oleate, an SCD1-generated MUFA, restored the gene expression related to fibrosis, cirrhosis, and HCC. Although SCD1 deficient mice are protected against obesity and fatty liver, our results show that MUFA deprivation results in liver injury, including fibrosis, thus providing novel insights between MUFA insufficiency and pathways leading to fibrosis, cirrhosis, and HCC under lean non-steatotic conditions.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 7","pages":"Article 159538"},"PeriodicalIF":3.9,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141787234","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}