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

{"title":"Hypoxia-inducible lipid droplet-associated protein (HILPDA) and cystathionine β-synthase (CBS) co-contribute to protecting intestinal epithelial cells from Staphylococcus aureus via regulating lipid droplets formation","authors":"Shaodong Fu ,&nbsp;Rui Yu ,&nbsp;Bo Yang ,&nbsp;Xiangan Han ,&nbsp;Yuanyuan Xu ,&nbsp;Jinfeng Miao","doi":"10.1016/j.bbalip.2024.159558","DOIUrl":"10.1016/j.bbalip.2024.159558","url":null,"abstract":"<div><p>Despite <em>Staphylococcus aureus</em> (<em>S. aureus</em>) being a highly studied zoontic bacterium, its enteropathogenicity remains elusive. Herein, our findings demonstrated that <em>S. aureus</em> infection led to the accumulation of lipid droplets (LDs) in intestinal epithelial cells, accompanied by marked elevation inflammatory response that ultimately decreases intracellular bacterial load. The aforestated phenomenon may be partly attributed to the up-regulation of hypoxia-inducible lipid droplet-associated protein (HILPDA) and the concomitant down-regulation of cystathionine β-synthase (CBS) protein. Moreover, <em>S. aureus</em> infection up-regulated the expression of HILPDA, thereby promoting LDs accumulation, and down-regulated that of CBS, consequently inhibiting microsomal triglyceride transfer protein (MTTP) expression. This process may suppress the transport of LDs to the extracellular environment, further contributing to the formation of intracellular LDs. In summary, the results of this study provide significant insights into the intricate mechanisms through which the host organism combats pathogens and maintains the balance of sulfur and lipid metabolism. These findings not only enhance our understanding of the host's defense mechanisms but also offer promising avenues for the development of novel strategies to combat intestinal infectious diseases.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 8","pages":"Article 159558"},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035121","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":"TMAO induces pyroptosis of vascular endothelial cells and atherosclerosis in ApoE−/− mice via MBOAT2-mediated endoplasmic reticulum stress","authors":"Bo Yu ,&nbsp;Chuchu Yuan ,&nbsp;Jinna Chen ,&nbsp;Zhixiang Zhou ,&nbsp;Yile Zhang ,&nbsp;Ming Su ,&nbsp;Dangheng Wei ,&nbsp;Peng Wu","doi":"10.1016/j.bbalip.2024.159559","DOIUrl":"10.1016/j.bbalip.2024.159559","url":null,"abstract":"<div><p>Trimethylamine N-oxide (TMAO), a metabolite produced by intestinal flora, is recognized as an independent risk factor for atherosclerosis and atherosclerotic cardiovascular diseases. However, the underlying mechanism remains poorly understood. Here, we showed that dietary TMAO supplementation accelerates atherosclerosis in ApoE^−/− mice. Pyroptosis and the expression of phospholipid-modifying enzyme MBOAT2 were increased in endothelial cells within atherosclerotic lesions. Genetic upregulation of MBOAT2 via adeno-associated virus with endothelium-specific promoter results in increased atherosclerotic lesions in ApoE^−/− mice. Mechanistically, the overexpression of MBOAT2 disrupted glycerophospholipid metabolism and induced endothelial cell pyroptosis in an Endoplasmic reticulum stress-dependent manner. These data reveal that TMAO promotes endothelial cell pyroptosis and the progression of atherosclerotic lesions through the upregulation of MBOAT2, indicating that MBOAT2 is a promising therapeutic target for atherosclerosis.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 8","pages":"Article 159559"},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046222","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":"Mapping lipid species remodeling in high fat diet-fed mice: Unveiling adipose tissue dysfunction with Raman microspectroscopy","authors":"Elnaz Sheikh ,&nbsp;Qianglin Liu ,&nbsp;David Burk ,&nbsp;William N. Beavers ,&nbsp;Xing Fu ,&nbsp;Manas Ranjan Gartia","doi":"10.1016/j.bbalip.2024.159557","DOIUrl":"10.1016/j.bbalip.2024.159557","url":null,"abstract":"<div><p>Dysregulated lipid metabolism in obesity leads to adipose tissue expansion, a major contributor to metabolic dysfunction and chronic disease. Lipid metabolism and fatty acid changes play vital roles in the progression of obesity. In this proof-of-concept study, Raman techniques combined with histochemical imaging methods were utilized to analyze the impact of a high-fat diet (HFD) on different types of adipose tissue in mice, using a small sample size (<em>n</em> = 3 per group). After six weeks of high-fat diet (HFD) feeding, our findings showed hypertrophy, elevated collagen levels, and increased macrophage presence in the adipose tissues of the HFD group compared to the low-fat diet (LFD) group. Statistical analysis of Raman spectra revealed significantly lower unsaturated lipid levels and higher lipid to protein content in different fat pads (brown adipose tissue (BAT), subcutaneous white adipose tissue (SWAT), and visceral white adipose tissue (VWAT)) with HFD. Raman images of adipose tissues were analyzed using Empty modeling and DCLS methods to spatially profile unsaturated and saturated lipid species in the tissues. It revealed elevated levels of ω-3, ω-6, cholesterol, and triacylglycerols in BAT adipose tissues of HFD compared to LFD tissues. These findings indicated that while cholesterol, ω-6/ω-3 ratio, and triacylglycerol levels have risen in the SWAT and VWAT adipose tissues of the HFD group, the levels of ω-3 and ω-6 have decreased following the HFD. The study showed that Raman spectroscopy provided invaluable information at the molecular level for investigating lipid species remodeling and spatial mapping of adipose tissues during HFD.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 8","pages":"Article 159557"},"PeriodicalIF":3.9,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916019","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":"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}