{"title":"Recent advances on the physiological and pathophysiological roles of polyunsaturated fatty acids and their biosynthetic pathway","authors":"Hyeon-Cheol Lee-Okada, Chengxuan Xue, Takehiko Yokomizo","doi":"10.1016/j.bbalip.2024.159564","DOIUrl":"10.1016/j.bbalip.2024.159564","url":null,"abstract":"<div><div>Polyunsaturated fatty acids (PUFAs)—fatty acids containing multiple double bonds within their carbon chain—are an indispensable component of the cell membrane. PUFAs, including the omega-6 PUFA arachidonic acid (ARA; C20:4n-6) and the omega-3 PUFAs eicosapentaenoic acid (EPA; C20:5n-3) and docosahexaenoic acid (DHA; C22:6n-3), have been implicated in various (patho)physiological events. These PUFAs are either obtained from the diet or biosynthesized from the essential fatty acids linoleic acid (LA; C18:2n-6) and α-linolenic acid (ALA; C18:3n-3) <em>via</em> enzymatic reactions that are catalyzed by fatty acid elongases (ELOVL2 and ELOVL5) and fatty acid desaturases (FADS1 and FADS2). In this review, we summarize the recent literature studying the role of PUFAs, placing a special emphasis on the newly discovered functions of PUFAs and their biosynthetic pathway as revealed by studies using animal models targeting the PUFA biosynthetic pathway and genetic approaches including genome-wide association studies.</div></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 1","pages":"Article 159564"},"PeriodicalIF":3.9,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324194","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}
Ning Ding, Yu Zhang, Jiayao Wang, Jianfeng Liu, Jing Zhang, Chun Zhang, Lei Zhou, Jinkang Cao, Li Jiang
{"title":"Lipidomic and transcriptomic characteristics of boar seminal plasma extracellular vesicles associated with sperm motility","authors":"Ning Ding, Yu Zhang, Jiayao Wang, Jianfeng Liu, Jing Zhang, Chun Zhang, Lei Zhou, Jinkang Cao, Li Jiang","doi":"10.1016/j.bbalip.2024.159561","DOIUrl":"10.1016/j.bbalip.2024.159561","url":null,"abstract":"<div><p>Seminal plasma extracellular vesicles (SPEVs) play an important role in regulating sperm motility by delivering various cargoes, such as miRNAs, mRNAs, proteins and metabolites. However, information on the lipid compositions of SPEVs and their roles in semen quality is limited. Here, we performed high-throughput transcriptomic and lipidomic analysis on SPEVs isolated from 20 boars with high or low sperm motility. Then, we evaluated the lipid composition and gene expression characteristics of SPEVs and identified the specific lipids and genes related to sperm motility. As a result, a total of 26 lipid classes were identified in SPEVs, and five subclasses, CerG2, CerG3, LPE, LPS and TG, were significantly different in boars with high and low sperm motility. In addition, 195 important lipids and 334 important genes were identified by weighted gene coexpression analysis (WGCNA) and differential expression analysis. We observed that several important genes and lipids in SPEVs potentially influence sperm motility via glycerophospholipid metabolism, glycerolipid metabolism, the sphingolipid signaling pathway and the ferroptosis pathway. Furthermore, we found a significant correlation between the content of 22 lipids and the expression levels of 67 genes (|cor| > 0.8, <em>P</em> < 0.05). Moreover, we observed that three important gene-lipid linkages (CerG1 (d22:0/24:0) - <em>RCAN3</em>, Cer (d18:1/24:0) - <em>SCFD2</em> and CerG1 (d18:0/24:1) - <em>SCFD2</em>) were strongly correlated with sperm motility. Based on the results, some genes and lipids in SPEVs may play important roles in sperm motility by interacting with sperm through important pathways.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 1","pages":"Article 159561"},"PeriodicalIF":3.9,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1388198124001112/pdfft?md5=866d0705aaf225c6174f73f4242897f6&pid=1-s2.0-S1388198124001112-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142128993","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}
Maria Soledad Hidrobo , Marcus Höring , Sarah Brunner , Gerhard Liebisch , Sabine Schweizer , Martin Klingenspor , Renate Schreiber , Rudolf Zechner , Ralph Burkhardt , Josef Ecker
{"title":"Cold-induced phosphatidylethanolamine synthesis in liver and brown adipose tissue of mice","authors":"Maria Soledad Hidrobo , Marcus Höring , Sarah Brunner , Gerhard Liebisch , Sabine Schweizer , Martin Klingenspor , Renate Schreiber , Rudolf Zechner , Ralph Burkhardt , Josef Ecker","doi":"10.1016/j.bbalip.2024.159562","DOIUrl":"10.1016/j.bbalip.2024.159562","url":null,"abstract":"<div><p>Increasing energy expenditure in brown adipose (BAT) tissue by cold-induced lipolysis is discussed as a potential strategy to counteract imbalanced lipid homeostasis caused through unhealthy lifestyle and cardiometabolic disease. Yet, it is largely unclear how liberated fatty acids (FA) are metabolized. We investigated the liver and BAT lipidome of mice housed for 1 week at thermoneutrality, 23 °C and 4 °C using quantitative mass spectrometry-based lipidomics. Housing at temperatures below thermoneutrality triggered the generation of phosphatidylethanolamine (PE) in both tissues. Particularly, the concentrations of PE containing polyunsaturated fatty acids (PUFA) in their acyl chains like PE 18:0_20:4 were increased at cold. Investigation of the plasma's FA profile using gas chromatography coupled to mass spectrometry revealed a negative correlation of PUFA with unsaturated PE in liver and BAT indicating a flux of FA from the circulation into these tissues. Beta-adrenergic stimulation elevated intracellular levels of PE 38:4 and PE 40:6 in beige wildtype adipocytes, but not in adipose triglyceride lipase (ATGL)-deficient cells. These results imply an induction of PE synthesis in liver, BAT and thermogenic adipocytes after activation of the beta-adrenergic signaling cascade.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1870 1","pages":"Article 159562"},"PeriodicalIF":3.9,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1388198124001124/pdfft?md5=6addaa8a37f255ac8fb4473b52a49bbf&pid=1-s2.0-S1388198124001124-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103952","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}
Jia Zhang, Tao Zhang, Yihang Chen, Xiaojie Xuan, Yuqian Zhao, Gaofeng Lu
{"title":"Spermidine mitigates ferroptosis in free fatty acid-induced AML-12 cells through the ATF4/SLC7A11/GCLM/GPX4 pathway","authors":"Jia Zhang, Tao Zhang, Yihang Chen, Xiaojie Xuan, Yuqian Zhao, Gaofeng Lu","doi":"10.1016/j.bbalip.2024.159560","DOIUrl":"10.1016/j.bbalip.2024.159560","url":null,"abstract":"<div><p>Non-alcoholic fatty liver disease (NAFLD) is a prominent cause of chronic liver disease worldwide. Spermidine (SPD), a naturally occurring polyamine, has shown potential in alleviating the accumulation of hepatic lipids and reducing NAFLD symptoms in overweight mice. Nonetheless, the specific mechanisms through which SPD exerts its effects remain largely unknown. This study seeks to explore the protective effects of SPD on NAFLD and to clarify the underlying mechanisms. An in vitro model of NAFLD was established by inducing steatosis in AML-12 cells through the use of free fatty acids (FFAs). Our experimental results demonstrate that SPD significantly reduces NAFLD development induced by FFAs. This reduction is primarily achieved through the inhibition of cellular ferroptosis, as evidenced by decreased levels of Fe<sup>2+</sup>, malondialdehyde (MDA), and reactive oxygen species (ROS). Additionally, SPD was found to enhance cellular activity and ameliorate mitochondrial dysfunction and oxidative stress caused by FFA exposure.</p><p>Further mechanistic studies have revealed that SPD upregulates the expression of solute transporter family 7a member 11 (SLC7A11), glutamate-cysteine ligase modifier subunit (GCLM), and glutathione peroxidase (GPX4). This upregulation is mediated by the activation of activating transcription factor 4 (ATF4). Knockdown experiments of ATF4 confirmed that its inhibition reverses the upregulation of SLC7A11, GCLM, and GPX4, thereby negating the protective effects of SPD. In conclusion, our findings suggest that SPD mitigates NAFLD by modulating the ATF4/SLC7A11/GCLM/GPX4 signaling pathway, resulting in the suppression of ferroptosis and the improvement of cellular health. These insights provide a novel molecular mechanism and identify potential therapeutic targets for the treatment of NAFLD.</p></div>","PeriodicalId":8815,"journal":{"name":"Biochimica et biophysica acta. Molecular and cell biology of lipids","volume":"1869 8","pages":"Article 159560"},"PeriodicalIF":3.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142049738","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}
Shaodong Fu , Rui Yu , Bo Yang , Xiangan Han , Yuanyuan Xu , Jinfeng Miao
{"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 , Rui Yu , Bo Yang , Xiangan Han , Yuanyuan Xu , 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}
Bo Yu , Chuchu Yuan , Jinna Chen , Zhixiang Zhou , Yile Zhang , Ming Su , Dangheng Wei , Peng Wu
{"title":"TMAO induces pyroptosis of vascular endothelial cells and atherosclerosis in ApoE−/− mice via MBOAT2-mediated endoplasmic reticulum stress","authors":"Bo Yu , Chuchu Yuan , Jinna Chen , Zhixiang Zhou , Yile Zhang , Ming Su , Dangheng Wei , 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<sup>−/−</sup> 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<sup>−/−</sup> 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}
Elnaz Sheikh , Qianglin Liu , David Burk , William N. Beavers , Xing Fu , Manas Ranjan Gartia
{"title":"Mapping lipid species remodeling in high fat diet-fed mice: Unveiling adipose tissue dysfunction with Raman microspectroscopy","authors":"Elnaz Sheikh , Qianglin Liu , David Burk , William N. Beavers , Xing Fu , 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, Gil-Soo Han, 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 Mg<sup>2+</sup>-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}
Martin Riecan , Veronika Domanska , Cristina Lupu , Maulin Patel , Michaela Vondrackova , Martin Rossmeisl , Alan Saghatelian , Florea Lupu , Ondrej Kuda
{"title":"Tissue-specific sex-dependent difference in the metabolism of fatty acid esters of hydroxy fatty acids","authors":"Martin Riecan , Veronika Domanska , Cristina Lupu , Maulin Patel , Michaela Vondrackova , Martin Rossmeisl , Alan Saghatelian , Florea Lupu , 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 , Siddabasave Gowda B. Gowda , Sidharth P. Mishra , Lipsa Rani Nath , Adewale James , Alisha Kulkarni , Yuktee Srikant , Rohitram Upendram , MathanKumar Marimuthu , Shu-Ping Hui , Shalini Jain , Kain Vasundhara , Hariom Yadav , 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}