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

{"title":"Integrator complex subunit 6 promotes hepatocellular steatosis via β-catenin-PPARγ axis","authors":"","doi":"10.1016/j.bbalip.2024.159532","DOIUrl":"10.1016/j.bbalip.2024.159532","url":null,"abstract":"<div><p>Hepatic adipogenesis has common mechanisms with adipocyte differentiation such as PPARγ involvement and the induction of adipose tissue-specific molecules. A previous report demonstrated that integrator complex subunit 6 (INTS6) is required for adipocyte differentiation. This study aimed to investigate INTS6 expression and its role in hepatic steatosis progression. The expression of INTS6 and PPARγ was examined in the liver of a mouse model of steatohepatitis and in paired liver biopsy samples from 11 patients with severe obesity and histologically proven metabolic dysfunction associated steatohepatitis (MASH) before and one year after bariatric surgery. To induce hepatocellular steatosis in vitro, an immortalized human hepatocyte cell line Hc3716 was treated with free fatty acids. In the steatohepatitis mouse model, we observed hepatic induction of INTS6, PPARγ, and adipocyte-specific genes. In contrast, β-catenin which negatively regulates PPARγ was reduced. Biopsied human livers demonstrated a strong positive correlation (r² = 0.8755) between INTS6 and PPARγ mRNA levels. After bariatric surgery, gene expressions of PPARγ, FABP4, and CD36 were mostly downregulated. In our in vitro experiments, we observed a concentration-dependent increase in Oil Red O staining in Hc3716 cells after treatment with the free fatty acids. Alongside this change, the expression of INTS6, PPARγ, and adipocyte-specific genes was induced. INTS6 knockdown using siRNA significantly suppressed cellular lipid accumulation together with induction of β-catenin and PPARγ downregulation. Collectively, INTS6 expression closely correlates with PPARγ. INTS6 suppression significantly reduced hepatocyte steatosis via β-catenin-PPARγ axis, indicating that INTS6 could be a novel therapeutic target for treating MASH.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 7","pages":"Article 159532"},"PeriodicalIF":3.9,"publicationDate":"2024-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562571","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":"Disruption of the peripheral biological clock may play a role in sleep deprivation-induced dysregulation of lipid metabolism in both the daytime and nighttime phases","authors":"Chufan Zhou ,&nbsp;Ziping Hu ,&nbsp;Xuan Liu ,&nbsp;Yuefan Wang ,&nbsp;Shougang Wei ,&nbsp;Zhifeng Liu","doi":"10.1016/j.bbalip.2024.159530","DOIUrl":"10.1016/j.bbalip.2024.159530","url":null,"abstract":"<div><h3>Study objectives</h3><p>This study aimed to examine the effect of sleep deprivation (SD) on lipid metabolism or lipid metabolism regulation in the liver and white adipose tissue (WAT) during the light and dark phases and <strong>explored the</strong> possible mechanisms underlying the diurnal effect of SD on lipid metabolism associated with clock genes.</p></div><div><h3>Methods</h3><p>Male C57BL/6J mice aged 2 months were deprived of sleep daily for 20 h for ten consecutive days with weakly forced locomotion. The body weights and food consumption levels of the SD and control mice were recorded, and the mice were then sacrificed at ZT (zeitgeber time) 2 and ZT 14. The peripheral clock genes, enzymes involved in fat synthesis and catabolism in the WAT, and melatonin signalling pathway-mediated lipid metabolism in the liver were assessed. Untargeted metabolomics and tandem mass tag (TMT) proteomics were used to identify differential lipid metabolism pathways in the liver.</p></div><div><h3>Results</h3><p>Bodyweight gain and daily food consumption were dramatically elevated after SD. Profound disruptions in the diurnal regulation of the hepatic peripheral clock and enzymes involved in fat synthesis and catabolism in the WAT were observed, with a strong emphasis on hepatic lipid metabolic pathways, while melatonin signalling pathway-mediated lipid metabolism exhibited moderate changes.</p></div><div><h3>Conclusions</h3><p>In mice, ten consecutive days of SD increased body weight gain and daily food consumption. In addition, SD profoundly disrupted lipid metabolism in the WAT and liver during the light and dark periods. These diurnal changes may be related to disorders of the peripheral biological clock.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 7","pages":"Article 159530"},"PeriodicalIF":3.9,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141533483","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":"Mammalian START-like phosphatidylinositol transfer proteins – Physiological perspectives and roles in cancer biology","authors":"","doi":"10.1016/j.bbalip.2024.159529","DOIUrl":"10.1016/j.bbalip.2024.159529","url":null,"abstract":"<div><p>PtdIns and its phosphorylated derivatives, the phosphoinositides, are the biochemical components of a major pathway of intracellular signaling in all eukaryotic cells. These lipids are few in terms of cohort of unique positional isomers, and are quantitatively minor species of the bulk cellular lipidome. Nevertheless, phosphoinositides regulate an impressively diverse set of biological processes. It is from that perspective that perturbations in phosphoinositide-dependent signaling pathways are increasingly being recognized as causal foundations of many human diseases – including cancer. Although phosphatidylinositol transfer proteins (PITPs) are not enzymes, these proteins are physiologically significant regulators of phosphoinositide signaling. As such, PITPs are conserved throughout the eukaryotic kingdom. Their biological importance notwithstanding, PITPs remain understudied. Herein, we review current information regarding PITP biology primarily focusing on how derangements in PITP function disrupt key signaling/developmental pathways and are associated with a growing list of pathologies in mammals.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 7","pages":"Article 159529"},"PeriodicalIF":3.9,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465921","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":"Lipid signature associated with chronic colon inflammation reveals a dysregulation in colonocyte differentiation process","authors":"Albert Maimó-Barceló ,&nbsp;Lucía Martín-Saiz ,&nbsp;Maria Barceló-Nicolau ,&nbsp;Simona Salivo ,&nbsp;Karim Pérez-Romero ,&nbsp;Ramon M. Rodriguez ,&nbsp;Javier Martín ,&nbsp;Marco A. Martínez ,&nbsp;Marcelo García ,&nbsp;Isabel Amengual ,&nbsp;Daniel Ginard ,&nbsp;José A. Fernández ,&nbsp;Gwendolyn Barceló-Coblijn","doi":"10.1016/j.bbalip.2024.159528","DOIUrl":"10.1016/j.bbalip.2024.159528","url":null,"abstract":"<div><p>Inflammatory Bowel Disease (IBD) comprises a heterogeneous group of chronic inflammatory conditions of the gastrointestinal tract that include ulcerative colitis (UC) and Crohn's disease. Although the etiology is not well understood, IBD is characterized by a loss of the normal epithelium homeostasis that disrupts the intestinal barrier of these patients. Previous work by our group demonstrated that epithelial homeostasis along the colonic crypts involves a tight regulation of lipid profiles. To evaluate whether lipidomic profiles conveyed the functional alterations observed in the colonic epithelium of IBD, we performed matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) analyses of endoscopic biopsies from inflamed and non-inflamed segments obtained from UC patients. Our results indicated that lipid profiling of epithelial cells discriminated between healthy and UC patients. We also demonstrated that epithelial cells of the inflamed mucosa were characterized by a decrease in mono- and di-unsaturated fatty acid-containing phospholipids and higher levels of arachidonic acid-containing species, suggesting an alteration of the lipid gradients occurring concomitantly to the epithelial differentiation. This result was reinforced by the immunofluorescence analysis of EPHB2 and HPGD, markers of epithelial cell differentiation, sustaining that altered lipid profiles were at least partially due to a faulty differentiation process. Overall, our results showed that lipid profiling by MALDI-MSI faithfully conveys molecular and functional alterations associated with the inflamed epithelium, providing the foundation for a novel molecular characterization of UC patients.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 7","pages":"Article 159528"},"PeriodicalIF":3.9,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465922","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":"Differentiating human phospholipase A2's activity toward phosphatidylinositol, phosphatidylinositol phosphate and phosphatidylinositol bisphosphate","authors":"Daiki Hayashi ,&nbsp;Edward A. Dennis","doi":"10.1016/j.bbalip.2024.159527","DOIUrl":"10.1016/j.bbalip.2024.159527","url":null,"abstract":"<div><p>Phospholipase A₂'s (PLA₂'s) constitute a superfamily of enzymes that hydrolyze the <em>sn</em>-2 fatty acyl chain on glycerophospholipids. We have previously reported that each PLA₂ Type shows a unique substrate specificity for the molecular species it hydrolyzes, especially the acyl chain that is cleaved from the <em>sn</em>-2 position and to some extent the polar group. However, phosphatidylinositol (PI) and PI phosphates (PIPs) have not been as well studied as substrates as other phospholipids because the PIPs require adaptation of the standard analysis methods, but they are important <em>in vivo</em>. We determined the <em>in vitro</em> activity of the three major types of human PLA₂'s, namely the cytosolic (c), calcium-independent (i), and secreted (s) PLA₂^'s toward PI, PI-4-phosphate (PI(4)P), and PI-4,5-bisphosphate (PI(4,5)P₂). The <em>in vitro</em> assay revealed that Group IVA cPLA₂ (GIVA cPLA₂) showed relatively high activity toward PI and PI(4)P among the tested PLA₂'s; nevertheless, the highly hydrophilic headgroup disrupted the interaction between the lipid surface and the enzyme. GIVA cPLA₂ and GVIA iPLA₂ showed detectable activity toward PI(4,5)P₂, but it appeared to be a poorer substrate for all of the PLA₂'s tested. Furthermore, molecular dynamics (MD) simulations demonstrated that Thr416 and Glu418 of GIVA cPLA₂ contribute significantly to accommodating the hydrophilic head groups of PI and PI(4)P, which could explain some selectivity for PI and PI(4)P. These results indicated that GIVA cPLA₂ can accommodate PI and PI(4)P in its active site and hydrolyze them, suggesting that the GIVA cPLA₂ may best account for the PI and PIP hydrolysis in living cells.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 7","pages":"Article 159527"},"PeriodicalIF":3.9,"publicationDate":"2024-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1388198124000775/pdfft?md5=23d286a293fc0a12ab4dc508fd26a0b7&pid=1-s2.0-S1388198124000775-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141452706","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":"Increased obesogenic action of palmitic acid during early stage of adipogenesis","authors":"Ewa Stanek ,&nbsp;Krzysztof Czamara ,&nbsp;Agnieszka Kaczor","doi":"10.1016/j.bbalip.2024.159525","DOIUrl":"10.1016/j.bbalip.2024.159525","url":null,"abstract":"<div><p>The functional differences between preadipocytes and fully differentiated mature adipocytes derived from stromal vascular fraction stem cells, as well as primary adipocytes have been analysed by evaluating their response to the obesogenic factor (a saturated fatty acid) and TNF-triggered inflammation. The analysis of single adipocytes shows that the saturated fatty acid (palmitic acid) accumulation is accompanied by inflammation and considerably dependent on the stage of the adipogenesis. In particular, preadipocytes show the exceptional potential for palmitic acid uptake resulting in their hypertrophy and the elevated cellular expression of the inflammation marker (ICAM-1). Our research provides new information on the impact of obesogenic factors on preadipocytes that is important in the light of childhood obesity prevention.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 7","pages":"Article 159525"},"PeriodicalIF":4.8,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1388198124000751/pdfft?md5=94478df13680f623ff6081e27a983da1&pid=1-s2.0-S1388198124000751-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320399","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":"Liver phospholipid fatty acid composition in response to chronic high-fat diets","authors":"Tamara Popović ,&nbsp;Aleksandra Nenadović ,&nbsp;Anica Stanković ,&nbsp;Jasmina Debeljak Martačić ,&nbsp;Slavica Ranković ,&nbsp;Sanjin Kovačević ,&nbsp;Jelena Nešović Ostojić ,&nbsp;Andjelija Ilić ,&nbsp;Jelena Milašin ,&nbsp;Silvio De Luka ,&nbsp;Alexander M. Trbovichch","doi":"10.1016/j.bbalip.2024.159526","DOIUrl":"10.1016/j.bbalip.2024.159526","url":null,"abstract":"<div><p>Liver phospholipid fatty acid composition depends on the dietary lipid intake and the efficiency of hepatic enzymatic activity. Our study aimed to simultaneously investigate the liver phospholipid fatty acid composition in response to chronic linseed, palm, or sunflower oil diets. We used adult female C57/BL6 mice and randomly divided them into control and three groups treated with 25 % dietary oils. Prior to treatment, we analyzed the fatty acid profiles in dietary oils and hepatocytes and, after 100 days, the fatty acid composition in the liver using gas-liquid chromatography. Linseed oil treatment elevated alpha-linolenic, eicosapentaenoic, and docosapentaenoic acids and reduced arachidonic and docosatetraenoic acids, consequently lowering the n-6/n-3 ratio. Palm oil treatment increased linoleic acid and decreased docosahexaenoic acid, contributing to an elevated n-6/n-3 ratio. Sunflower oil treatment elevated total monounsaturated fatty acids by increasing palmitoleic, oleic, and vaccenic acids. The estimated activity of Δ9 desaturase was significantly elevated in the sunflower oil group, while Δ5 desaturase was the highest, and Δ6 desaturase was the lowest after the linseed oil diet. Our findings demonstrate that chronic consumption of linseed, palm, or sunflower oil alters the distribution of liver phospholipid fatty acids differently. Sunflower oil diet elevated total monounsaturated fatty acids, proposing potential benefits for liver tissue health. Considering these outcomes, a substantial recommendation emerges to elevate linseed oil intake, recognized as the principal ALA source, thereby aiding in reducing the n-6/n-3 ratio. Moreover, modifying dietary habits to incorporate specific vegetable oils in daily consumption could substantially enhance overall health.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 7","pages":"Article 159526"},"PeriodicalIF":4.8,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316612","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":"Lipid droplets control the negative effect of non-yeast sterols in membranes of Saccharomyces cerevisiae under hypoxic stress","authors":"Lívia Petrisková ,&nbsp;Marie Kodedová ,&nbsp;Mária Balážová ,&nbsp;Hana Sychrová ,&nbsp;Martin Valachovič","doi":"10.1016/j.bbalip.2024.159523","DOIUrl":"10.1016/j.bbalip.2024.159523","url":null,"abstract":"<div><p>The effectivity of utilization of exogenous sterols in the yeast <em>Saccharomyces cerevisiae</em> exposed to hypoxic stress is dependent on the sterol structure. The highly imported sterols include animal cholesterol or plant sitosterol, while ergosterol, typical of yeasts, is imported to a lesser extent. An elevated utilization of non-yeast sterols is associated with their high esterification and relocalization to lipid droplets (LDs). Here we present data showing that LDs and sterol esterification play a critical role in the regulation of the accumulation of non-yeast sterols in membranes. Failure to form LDs during anaerobic growth in media supplemented with cholesterol or sitosterol resulted in an extremely long lag phase, in contrast to normal growth in media with ergosterol or plant stigmasterol. Moreover, in <em>hem1</em>∆, which mimics anaerobiosis, neither cholesterol nor sitosterol supported the growth in an LD-less background. The incorporation of non-ergosterol sterols into the membranes affected fundamental membrane characteristics such as relative membrane potential, permeability, tolerance to osmotic stress and the formation of membrane domains. Our findings reveal that LDs assume an important role in scenarios wherein cells are dependent on the utilization of exogenous lipids, particularly under anoxia. Given the diverse lipid structures present in yeast niches, LDs fulfil a protective role, mitigating the risk of excessive accumulation of potentially toxic steroids and fatty acids in the membranes. Finally, we present a novel function for sterols in a model eukaryotic cell – alleviation of the lipotoxicity of unsaturated fatty acids.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 7","pages":"Article 159523"},"PeriodicalIF":4.8,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309846","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":"Protective effects of fatty acid amide hydrolase inhibition in UVB-activated microglia","authors":"Veronica Carnicelli ,&nbsp;Noemi De Dominicis ,&nbsp;Lucia Scipioni ,&nbsp;Marina Fava ,&nbsp;Federico Fanti ,&nbsp;Benedetta Cinque ,&nbsp;Alessandro Leuti ,&nbsp;Clotilde Beatrice Angelucci ,&nbsp;Anna Rita Lizzi ,&nbsp;Roberto Giacominelli-Stuffler ,&nbsp;Vincenzo Flati ,&nbsp;Manuel Sergi ,&nbsp;Dario Compagnone ,&nbsp;Anna Maria Sardanelli ,&nbsp;Annamaria Tisi ,&nbsp;Sergio Oddi ,&nbsp;Mauro Maccarrone","doi":"10.1016/j.bbalip.2024.159524","DOIUrl":"10.1016/j.bbalip.2024.159524","url":null,"abstract":"<div><p>Neuroinflammation is a hallmark of several neurodegenerative disorders that has been extensively studied in recent years. Microglia, the primary immune cells of the central nervous system (CNS), are key players in this physiological process, demonstrating a remarkable adaptability in responding to various stimuli in the eye and the brain. Within the complex network of neuroinflammatory signals, the fatty acid <em>N</em>-ethanolamines, in particular <em>N</em>-arachidonylethanolamine (anandamide, AEA), emerged as crucial regulators of microglial activity under both physiological and pathological states. In this study, we interrogated for the first time the impact of the signaling of these bioactive lipids on microglial cell responses to a sub-lethal acute UVB radiation, a physical stressor responsible of microglia reactivity in either the retina or the brain. To this end, we developed an in vitro model using mouse microglial BV-2 cells. Upon 24 h of UVB exposure, BV-2 cells showed elevated oxidative stress markers and, cyclooxygenase (COX-2) expression, enhanced phagocytic and chemotactic activities, along with an altered immune profiling. Notably, UVB exposure led to a selective increase in expression and activity of fatty acid amide hydrolase (FAAH), the main enzyme responsible for degradation of fatty acid ethanolamides. Pharmacological FAAH inhibition via URB597 counteracted the effects of UVB exposure, decreasing tumor necrosis factor α (TNF-α) and nitric oxide (NO) release and reverting reactive oxidative species (ROS), interleukin-1β (IL-1β), and interleukin-10 (IL-10) levels to the control levels. Our findings support the potential of enhanced fatty acid amide signaling in mitigating UVB-induced cellular damage, paving the way to further exploration of these lipids in light-induced immune responses.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 7","pages":"Article 159524"},"PeriodicalIF":4.8,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S138819812400074X/pdfft?md5=a719f7b85c12fa8d0480943216d757a8&pid=1-s2.0-S138819812400074X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141299919","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":"The lipid side of unfolded protein response","authors":"Wojciech Białek ,&nbsp;Anita Hryniewicz-Jankowska ,&nbsp;Paulina Czechowicz ,&nbsp;Jakub Sławski ,&nbsp;James F. Collawn ,&nbsp;Aleksander Czogalla ,&nbsp;Rafał Bartoszewski","doi":"10.1016/j.bbalip.2024.159515","DOIUrl":"10.1016/j.bbalip.2024.159515","url":null,"abstract":"<div><p>Although our current knowledge of the molecular crosstalk between the ER stress, the unfolded protein response (UPR), and lipid homeostasis remains limited, there is increasing evidence that dysregulation of either protein or lipid homeostasis profoundly affects the other. Most research regarding UPR signaling in human diseases has focused on the causes and consequences of disrupted protein folding. The UPR itself consists of very complex pathways that function to not only maintain protein homeostasis, but just as importantly, modulate lipid biogenesis to allow the ER to adjust and promote cell survival. Lipid dysregulation is known to activate many aspects of the UPR, but the complexity of this crosstalk remains a major research barrier. ER lipid disequilibrium and lipotoxicity are known to be important contributors to numerous human pathologies, including insulin resistance, liver disease, cardiovascular diseases, neurodegenerative diseases, and cancer. Despite their medical significance and continuous research, however, the molecular mechanisms that modulate lipid synthesis during ER stress conditions, and their impact on cell fate decisions, remain poorly understood. Here we summarize the current view on crosstalk and connections between altered lipid metabolism, ER stress, and the UPR.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 7","pages":"Article 159515"},"PeriodicalIF":4.8,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1388198124000659/pdfft?md5=e64abfeac4129cb60c6ee6585091c8ae&pid=1-s2.0-S1388198124000659-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141282916","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}