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

{"title":"SIRT1/AMPK-mediated pathway: Ferulic acid from sugar beet pulp mitigating obesity-induced diabetes-linked complications and improving metabolic health","authors":"Sangeetha S.B. Singh,&nbsp;K. Neelakanteshwar Patil","doi":"10.1016/j.bbalip.2024.159511","DOIUrl":"10.1016/j.bbalip.2024.159511","url":null,"abstract":"<div><p>Obesity-induced type 2 diabetes (T2D) increases the risk of metabolic syndrome due to the high calorie intake. The role of sugar beet pulp (SBP) in T2D and the mechanism of its action remain unclear, though it is abundant in phenolics and has antioxidant activity. In this study, we isolated and purified ferulic acid from SBP, referred to as SBP-E, and studied the underlying molecular mechanisms in the regulation of glucose and lipid metabolism developing high glucose/high fat diet-induced diabetic models <em>in vitro</em> and <em>in vivo</em>. SBP-E showed no cytotoxicity and reduced the oxidative stress by increasing glutathione (GSH) in human liver (HepG2) and rat skeletal muscle (L6) cells. It also decreased body weight gain, food intake, fasting blood glucose levels (FBGL), glucose intolerance, hepatic steatosis, and lipid accumulation. Additionally, SBP-E decreased the oxidative stress and improved the antioxidant enzyme levels in high-fat diet (HFD)-induced T2D mice. Further, SBP-E reduced plasma and liver advanced glycation end products (AGEs), malondialdehyde (MDA), and pro-inflammatory cytokines, and increased anti-inflammatory cytokines in HFD-fed mice. Importantly, SBP-E significantly elevated AMPK, glucose transporter, SIRT1 activity, and Nrf2 expression and decreased ACC activity and SREBP1 levels in diabetic models. Collectively, our study results suggest that SBP-E treatment can improve obesity-induced T2D by regulating glucose and lipid metabolism via SIRT1/AMPK signalling and the AMPK/SREBP1/ACC1 pathway.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 7","pages":"Article 159511"},"PeriodicalIF":3.9,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955512","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":"Sterol O-acyltransferase (SOAT/ACAT) activity is required to form cholesterol crystals in hepatocyte lipid droplets","authors":"Jordan A. Bairos ,&nbsp;Uche Njoku ,&nbsp;Maria Zafar ,&nbsp;May G. Akl ,&nbsp;Lei Li ,&nbsp;Gunes Parlakgul ,&nbsp;Ana Paula Arruda ,&nbsp;Scott B. Widenmaier","doi":"10.1016/j.bbalip.2024.159512","DOIUrl":"10.1016/j.bbalip.2024.159512","url":null,"abstract":"<div><h3>Objective</h3><p>Excess cholesterol storage can induce the formation of cholesterol crystals in hepatocyte lipid droplets. Such crystals distinguish metabolic dysfunction associated steatohepatitis (MASH) from simple steatosis and may underlie its pathogenesis by causing cell damage that triggers liver inflammation. The mechanism linking cholesterol excess to its crystallization in lipid droplets is unclear. As cholesteryl esters localize to and accumulate in lipid droplets more readily than unesterified free cholesterol, we investigated whether cholesterol esterification by sterol O-acyltransferase (SOAT), also known as acyl co-A cholesterol acyltransferase (ACAT), is required for hepatocyte lipid droplet crystal formation.</p></div><div><h3>Method</h3><p>Cholesterol crystals were measured in cholesterol loaded Hep3B hepatocytes, RAW264.7 macrophages, and mouse liver using polarizing light microscopy. We examined the effect of blocking SOAT activity on crystal formation and compared these results to features of cholesterol metabolism and the progression to intracellular crystal deposits.</p></div><div><h3>Results</h3><p>Cholesterol loading of Hep3B cells caused robust levels of lipid droplet localized crystal formation in a dose- and time-dependent manner. Co-treatment with SOAT inhibitors and genetic ablation of <em>SOAT1</em> blocked crystal formation. SOAT inhibitor also blocked crystal formation in low density lipoprotein (LDL) treated Hep3B cells, acetylated LDL treated RAW 264.7 macrophages, and in the liver of mice genetically predisposed to hepatic cholesterol overload and in mice with cholesterol enriched diet-induced MASH.</p></div><div><h3>Conclusion</h3><p>SOAT1-mediated esterification may underlie cholesterol crystals associated with MASH by concentrating it in lipid droplets. These findings imply that inhibiting hepatocyte SOAT1 may be able to alleviate cholesterol associated MASH. Moreover, that either a lipid droplet localized cholesteryl ester hydrolase is required for cholesterol crystal formation, or the crystals are composed of cholesteryl ester.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 6","pages":"Article 159512"},"PeriodicalIF":4.8,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1388198124000623/pdfft?md5=6ae20c50190534efe47379a32a0424e1&pid=1-s2.0-S1388198124000623-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955515","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":"Elucidation of molecular mechanisms by which amyloid β1–42 fibrils exert cell toxicity","authors":"Kiryl Zhaliazka ,&nbsp;Dmitry Kurouski","doi":"10.1016/j.bbalip.2024.159510","DOIUrl":"10.1016/j.bbalip.2024.159510","url":null,"abstract":"<div><p>Abrupt aggregation of amyloid β₁_–₄₂ (Aβ₁_–₄₂) peptide in the frontal lobe is the expected underlying cause of Alzheimer's disease (AD). β-Sheet-rich oligomers and fibrils formed by Aβ₁_–₄₂ exert high cell toxicity. A growing body of evidence indicates that lipids can uniquely alter the secondary structure and toxicity of Aβ₁_–₄₂ aggregates. At the same time, underlying molecular mechanisms that determine this difference in toxicity of amyloid aggregates remain unclear. Using a set of molecular and biophysical assays to determine the molecular mechanism by which Aβ₁_–₄₂ aggregates formed in the presence of cholesterol, cardiolipin, and phosphatidylcholine exert cell toxicity. Our findings demonstrate that rat neuronal cells exposed to Aβ₁_–₄₂ fibrils formed in the presence of lipids with different chemical structure exert drastically different magnitude and dynamic of unfolded protein response (UPR) in the endoplasmic reticulum (ER) and mitochondria (MT). We found that the opposite dynamics of UPR in MT and ER in the cells exposed to Aβ₁_–₄₂: cardiolipin fibrils and Aβ₁_–₄₂ aggregates formed in a lipid-free environment. We also found that Aβ₁_–₄₂: phosphatidylcholine fibrils upregulated ER UPR simultaneously downregulating the UPR response of MT, whereas Aβ₁_–₄₂: cholesterol fibrils suppressed the UPR response of ER and upregulated UPR response of MT. We also observed progressively increasing ROS production that damages mitochondrial membranes and other cell organelles, ultimately leading to cell death.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 6","pages":"Article 159510"},"PeriodicalIF":4.8,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955511","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 versatile CYP74 clan enzyme CYP440A19 from the European lancelet Branchiostoma lanceolatum biosynthesizes novel macrolactone, epoxydiene, and related oxylipins","authors":"Elena O. Smirnova ,&nbsp;Natalia V. Lantsova ,&nbsp;Mats Hamberg ,&nbsp;Yana Y. Toporkova ,&nbsp;Alexander N. Grechkin","doi":"10.1016/j.bbalip.2024.159507","DOIUrl":"10.1016/j.bbalip.2024.159507","url":null,"abstract":"<div><p>The present work reports the detection and cloning of a new CYP74 clan gene of the European lancelet (<em>Branchiostoma lanceolatum</em>) and the biochemical characterization of the recombinant protein CYP440A19. CYP440A19 possessed epoxyalcohol synthase (EAS) activity towards the 13-hydroperoxides of linoleic and α-linolenic acids, which were converted into oxiranylcarbinols, i.e., (11<em>S</em>,12<em>R</em>,13<em>S</em>)-11-hydroxy-12,13-epoxy derivatives. The conversion of 9-hydroperoxides produced distinct products. Linoleic acid 9(<em>S</em>)-hydroperoxide (9-HPOD) was mainly converted into 9,14-diol (10<em>E</em>,12<em>E</em>)-9,14-dihydroxy-10,12-octadecadienoic acid and macrolactone 9(<em>S</em>),10(<em>R</em>)-epoxy-11(<em>E</em>)-octadecen-13(<em>S</em>)-olide. In addition, (8<em>Z</em>)-colneleic acid was formed. Brief incubations of the enzyme with 9-HPOD in a biphasic system of hexane–water enabled the isolation of the short-lived 9,10-epoxydiene (9<em>S</em>,10<em>R</em>,11<em>E</em>,13<em>E</em>)-9,10-epoxy-11,13-octadecadienoic acid. The structure and stereochemistry of the epoxyalcohols, macrolactone, (8<em>Z</em>)-colneleic acid (Me), and 9,10-epoxydiene (Me) were confirmed by ¹H-NMR, ¹H-¹H-COSY, ¹H-¹³C-HSQC, and ¹H-¹³C-HMBC spectroscopy. Macrolactone and <em>cis</em>-9,10-epoxydiene are novel products. The 9-hydroperoxide of α-linolenic acid was mainly converted into macrolactone 9(<em>S</em>),10(<em>R</em>)-epoxy-11(<em>E</em>),15(<em>Z</em>)-octadecadiene-13(<em>S</em>)-olide and a minority of divinyl ethers, particularly (8<em>Z</em>)-colnelenic acid. The versatility of enzyme catalysis, as well as the diversity of CYP74s and other enzymes involved in oxylipin biosynthesis, demonstrates the complexity of the lipoxygenase pathway in lancelets.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 6","pages":"Article 159507"},"PeriodicalIF":4.8,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916009","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":"Yeast perilipin Pet10p/Pln1p interacts with Erg6p in ergosterol metabolism","authors":"Martina Garaiova ,&nbsp;Yunfeng Ding ,&nbsp;Roman Holic ,&nbsp;Martin Valachovic ,&nbsp;Congyan Zhang ,&nbsp;Ivan Hapala ,&nbsp;Pingsheng Liu","doi":"10.1016/j.bbalip.2024.159506","DOIUrl":"10.1016/j.bbalip.2024.159506","url":null,"abstract":"<div><p>Lipid droplets (LD) are highly dynamic organelles specialized for the regulation of energy storage and cellular homeostasis. LD consist of a neutral lipid core surrounded by a phospholipid monolayer membrane with embedded proteins, most of which are involved in lipid homeostasis. In this study, we focused on one of the major LD proteins, sterol C24-methyltransferase, encoded by <em>ERG6</em>. We found that the absence of Erg6p resulted in an increased accumulation of yeast perilipin Pet10p in LD, while the disruption of <em>PET10</em> was accompanied by Erg6p LD over-accumulation. An observed reciprocal enrichment of Erg6p and Pet10p in <em>pet10Δ</em> and <em>erg6Δ</em> mutants in LD, respectively, was related to specific functional changes in the LD and was not due to regulation on the expression level. The involvement of Pet10p in neutral lipid homeostasis was observed in experiments that focused on the dynamics of neutral lipid mobilization as time-dependent changes in the triacylglycerols (TAG) and steryl esters (SE) content. We found that the kinetics of SE hydrolysis was reduced in <em>erg6Δ</em> cells and the mobilization of SE was completely lost in mutants that lacked both Erg6p and Pet10p. In addition, we observed that decreased levels of SE in <em>erg6Δpet10Δ</em> was linked to an overexpression of steryl ester hydrolase Yeh1p. Lipid analysis of <em>erg6Δpet10Δ</em> showed that <em>PET10</em> deletion altered the composition of ergosterol intermediates which had accumulated in <em>erg6Δ</em>. In conclusion, yeast perilipin Pet10p functionally interacts with Erg6p during the metabolism of ergosterol.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 6","pages":"Article 159506"},"PeriodicalIF":4.8,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1388198124000568/pdfft?md5=e7752e3ecc79495edbc30382d1b70985&pid=1-s2.0-S1388198124000568-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140908032","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":"Cytotoxic potential and metabolomic profiling of alkaloid rich fraction of Tylophora indica leaves","authors":"Mohd Adnan Kausar ,&nbsp;Shabana Parveen ,&nbsp;Sadaf Anwar ,&nbsp;Sadaf ,&nbsp;Sheersh Massey ,&nbsp;Hemat El-Sayed El-Horany ,&nbsp;Farida Habib Khan ,&nbsp;Mona Shahein ,&nbsp;Syed Akhtar Husain","doi":"10.1016/j.bbalip.2024.159505","DOIUrl":"10.1016/j.bbalip.2024.159505","url":null,"abstract":"<div><p><em>Tylophora indica</em> (Burm f.) Merrill, belong to family Asclepiadaceae, is considered to be a natural remedy with high medicinal benefits. The objective of this work is to assess the metabolomic profile of <em>T. indica</em> leaves enriched in alkaloids, as well as to evaluate the <em>in vitro</em> cytotoxicity of these leaves using the MTT assay on human breast MCF-7 and liver HepG2 cancer cell lines. Dried leaves of <em>T. indica</em> were extracted by sonication, using methanol containing 2 % (<em>v</em>/v) of acetic acid and obtained fraction was characterized by HPTLC and UPLC-MS. The UPLC-MS study yielded a preliminary identification of 32 metabolites, with tylophorine, tylophorine B, tylophorinine, and tylophorinidine being the predominant metabolites. The cytotoxicity of the extract of <em>T. indica</em> was evaluated on HepG2 and MCF-7 cell lines, yielding inhibitory concentration (IC₅₀) values of 75.71 μg/mL and 69.60 μg/mL, respectively. Data suggested that the phytochemical screening clearly showed presence of numerous secondary metabolites with moderate cytotoxic efficacy. In conclusion, the future prospects of <em>T. indica</em> appear promising for the advancement of phytopharmaceutical-based anticancer medications, as well as for the design of contemporary pharmaceuticals in the field of cancer chemotherapy.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 6","pages":"Article 159505"},"PeriodicalIF":4.8,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140903474","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":"A complete biosynthetic pathway of the long-chain polyunsaturated fatty acids in an amphidromous fish, ayu sweetfish Plecoglossus altivelis (Stomiati; Osmeriformes)","authors":"Bo Zhao ,&nbsp;Yingying Peng ,&nbsp;Yuki Itakura ,&nbsp;Myriam Lizanda ,&nbsp;Yutaka Haga ,&nbsp;Shuichi Satoh ,&nbsp;Juan C. Navarro ,&nbsp;Óscar Monroig ,&nbsp;Naoki Kabeya","doi":"10.1016/j.bbalip.2024.159498","DOIUrl":"https://doi.org/10.1016/j.bbalip.2024.159498","url":null,"abstract":"<div><p>The biosynthetic capability of the long-chain polyunsaturated fatty acids (LC-PUFA) in teleosts are highly diversified due to evolutionary events such as gene loss and subsequent neo- and/or sub-functionalisation of enzymes encoded by existing genes. In the present study, we have comprehensively characterised genes potentially involved in LC-PUFA biosynthesis, namely one front-end desaturase (<em>fads2</em>) and eight fatty acid elongases (<em>elovl1a</em>, <em>elovl1b</em>, <em>elovl4a</em>, <em>elovl4b</em>, <em>elovl5</em>, <em>elovl7</em>, <em>elovl8a</em> and <em>elovl8b</em>) from an amphidromous teleost, Ayu sweetfish, <em>Plecoglossus altivelis</em>. Functional analysis confirmed Fads2 with Δ6, Δ5 and Δ8 desaturase activities towards multiple PUFA substrates and several Elovl enzymes exhibited elongation capacities towards C_18–20 or C_18–22 PUFA substrates. Consequently, <em>P. altivelis</em> possesses a complete enzymatic capability to synthesise physiologically important LC-PUFA including arachidonic acid (ARA, 20:4n-6), eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) from their C₁₈ precursors. Interestingly, the loss of <em>elovl2</em> gene in <em>P. altivelis</em> was corroborated by genomic and phylogenetic analyses. However, this constraint would possibly be overcome by the function of alternative Elovl enzymes, such as Elovl1b, which has not hitherto been functionally characterised in teleosts. The present study contributes novel insights into LC-PUFA biosynthesis in the relatively understudied teleost group, Osmeriformes (Stomiati), thereby enhancing our understanding of the complement of LC-PUFA biosynthetic genes within teleosts.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 6","pages":"Article 159498"},"PeriodicalIF":4.8,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140824817","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":"Alterations in lipid metabolism accompanied by changes in protein and carotenoid content as spectroscopic markers of human T cell activation","authors":"Aleksandra Borek-Dorosz ,&nbsp;Anna Maria Nowakowska ,&nbsp;Paulina Laskowska ,&nbsp;Maciej Szydłowski ,&nbsp;William Tipping ,&nbsp;Duncan Graham ,&nbsp;Katarzyna Wiktorska ,&nbsp;Przemyslaw Juszczynski ,&nbsp;Malgorzata Baranska ,&nbsp;Piotr Mrowka ,&nbsp;Katarzyna Majzner","doi":"10.1016/j.bbalip.2024.159496","DOIUrl":"10.1016/j.bbalip.2024.159496","url":null,"abstract":"<div><p>This work aims to understand better the mechanism of cellular processes accompanying the activation of human T cells and to develop a novel, fast, label-free approach to identify molecular biomarkers for this process. The standard methodology for confirming the activation state of T cells is based on flow cytometry and using antibodies recognizing activation markers. The method provide high specificity detection but may be susceptible to background staining or non-specific secondary antibody reactions. Here, we evaluated the potential of Raman-based molecular imaging in distinguishing non-activated and activated human T cells. Confocal Raman microscopy was performed on T cells followed by chemometrics to obtain comprehensive molecular information, while Stimulated Raman Scattering imaging was used to quickly provide high-resolution images of selected cellular components of activated and non-activated cells. For the first time, carotenoids, lipids, and proteins were shown to be important biomarkers of T-cell activation. We found that T-cell activation was accompanied by lipid accumulation and loss of carotenoid content. Our findings on the biochemical, morphological, and structural changes associated with activated mature T cells provide insights into the molecular changes that occur during therapeutic manipulation of the immune response. The methodology for identifying activated T cells is based on a novel imaging method and supervised and unsupervised chemometrics. It unambiguously identifies specific and unique molecular changes without the need for staining, fixation, or any other sample preparation.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 5","pages":"Article 159496"},"PeriodicalIF":4.8,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140757040","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":"Total flavonoids of Broussonetia papyrifera alleviate non-alcohol fatty liver disease via regulating Nrf2/AMPK/mTOR signaling pathways","authors":"Qi Wang ,&nbsp;Yunfei Wei ,&nbsp;Yeling Wang ,&nbsp;Ziyang Yu ,&nbsp;Haiyan Qin ,&nbsp;Lilei Zhao ,&nbsp;Jiaqi Cheng ,&nbsp;Bingyu Shen ,&nbsp;Meiyu Jin ,&nbsp;Haihua Feng","doi":"10.1016/j.bbalip.2024.159497","DOIUrl":"https://doi.org/10.1016/j.bbalip.2024.159497","url":null,"abstract":"<div><h3>Backgrounds</h3><p>Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver diseases. The leaves of <em>Broussonetia papyrifera</em> contain a large number of flavonoids, which have a variety of biological functions.</p></div><div><h3>Methods</h3><p>In vitro experiments, free fatty acids were used to stimulate HepG2 cells. NAFLD model was established in vivo in mice fed with high fat diet (HFD) or intraperitoneally injected with Tyloxapol (Ty). At the same time, Total flavonoids of <em>Broussonetia papyrifera</em> (TFBP) was used to interfere with HepG2 cells or mice.</p></div><div><h3>Results</h3><p>The results showed that TFBP significantly decreased the lipid accumulation induced by oil acid (OA) with palmitic acid (PA) in HepG2 cells. TFBP decreased the total cholesterol (TC), the triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and increased high-density lipoprotein cholesterol (HDL<img>C) in serum. TFBP could also effectively inhibit the generation of reactive oxygen species (ROS) and restrained the level of myeloperoxidase (MPO), and enhance the activity of superoxide dismutase (SOD) to alleviate the injury from oxidative stress in the liver. Additionally, TFBP activated nuclear factor erythroid-2-related factor 2 (Nrf2) pathway to increasing the phosphorylation of AMP-activated protein kinase (AMPK). Meanwhile, protein levels of mTORC signaling pathway were evidently restrained with the treatment of TFBP.</p></div><div><h3>Conclusion</h3><p>Our experiments proved that TFBP has the therapeutic effect in NAFLD, and the activation of Nrf2 and AMPK signaling pathways should make sense.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 5","pages":"Article 159497"},"PeriodicalIF":4.8,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140633147","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":"Sea cucumber plasmalogen enhance lipophagy to alleviate abnormal lipid accumulation induced by high-fat diet","authors":"Zhigao Wang ,&nbsp;Yanjun Liu ,&nbsp;Xiaoxu Wang ,&nbsp;Xincen Wang ,&nbsp;Yuan Wu ,&nbsp;Yu Song ,&nbsp;Jie Xu ,&nbsp;Changhu Xue","doi":"10.1016/j.bbalip.2024.159495","DOIUrl":"https://doi.org/10.1016/j.bbalip.2024.159495","url":null,"abstract":"<div><p>Sea cucumber phospholipids, including the plasmalogen (PlsEtn) and plasmanylcholine (PakCho), have been shown to play a regulatory role in lipid metabolism disorders, but their mechanism of action remains unclear. Therefore, high-fat diet (HFD) and palmitic acid were used to establish lipid accumulation models in mice and HepG2 cells, respectively. Results showed that PlsEtn can reduce lipid deposition both <em>in vivo</em> and <em>in vitro</em>. HFD stimulation abnormally activated lipophagy through the phosphorylation of the AMPK/ULK1 pathway. The lipophagy flux monitor revealed abnormalities in the fusion stage of lipophagy. Of note, only PlsEtn stimulated the dynamic remodeling of the autophagosome membrane, which was indicated by the significantly decreased LC3 II/I ratio and p62 level. In all experiments, the effect of PlsEtn was significantly higher than that of PakCho. These findings elucidated the mechanism of PlsEtn in alleviating lipid accumulation, showed that it might be a lipophagy enhancer, and provided new insights into the high-value utilization of sea cucumber as an agricultural resource.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 5","pages":"Article 159495"},"PeriodicalIF":4.8,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140551336","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}