{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T23:25:21Z","timestamp":1793229921766,"version":"4.5.0"},"reference-count":60,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T00:00:00Z","timestamp":1680220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","doi-asserted-by":"publisher","award":["KI702"],"award-info":[{"award-number":["KI702"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Saarland University","award":["KI702"],"award-info":[{"award-number":["KI702"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>(1) Background: Aging is linked to an altered immune response and metabolism. Inflammatory conditions, such as sepsis, COVID-19, and steatohepatitis are more prevalent in the elderly and steatosis is linked both to severe COVID-19 and sepsis. We hypothesized that aging is linked to a loss of endotoxin tolerance, which normally protects the host from excessive inflammation, and that this is accompanied by elevated levels of hepatic lipids. (2) Methods: An in vivo lipopolysaccharide (LPS) tolerance model in young and old mice was used and the cytokine serum levels were measured by ELISA. Cytokine and toll-like receptor gene expression was determined by qPCR in the lungs and the liver; hepatic fatty acid composition was assessed by GC\u2013MS. (3) Results: The old mice showed a distinct potential for endotoxin tolerance as suggested by the serum cytokine levels and gene expression in the lung tissue. Endotoxin tolerance was less pronounced in the livers of the aged mice. However, the fatty acid composition strongly differed in the liver tissues of the young and old mice with a distinct change in the ratio of C18 to C16 fatty acids. (4) Conclusions: Endotoxin tolerance is maintained in advanced age, but changes in the metabolic tissue homeostasis may lead to an altered immune response in old individuals.<\/jats:p>","DOI":"10.3390\/biology12040530","type":"journal-article","created":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T02:08:01Z","timestamp":1680228481000},"page":"530","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Endotoxin Tolerance Acquisition and Altered Hepatic Fatty Acid Profile in Aged Mice"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4374-9607","authenticated-orcid":false,"given":"Amanda A.","family":"Wiesenthal","sequence":"first","affiliation":[{"name":"Pharmaceutical Biology, Department of Pharmacy, Saarland University, Campus C2.3, D-66123 Saarbr\u00fccken, Germany"},{"name":"Marine Biology, Institute of Biological Sciences, University of Rostock, D-18059 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0859-7773","authenticated-orcid":false,"given":"Thierry M.","family":"Legroux","sequence":"additional","affiliation":[{"name":"Pharmaceutical Biology, Department of Pharmacy, Saarland University, Campus C2.3, D-66123 Saarbr\u00fccken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Richter","sequence":"additional","affiliation":[{"name":"Biosynthesis of Active Substances, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, D-06120 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn H.","family":"Junker","sequence":"additional","affiliation":[{"name":"Biosynthesis of Active Substances, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, D-06120 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3390-9619","authenticated-orcid":false,"given":"Anne","family":"Hecksteden","sequence":"additional","affiliation":[{"name":"Institute of Sports and Preventive Medicine, Saarland University, D-66123 Saarbr\u00fccken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja M.","family":"Kessler","sequence":"additional","affiliation":[{"name":"Experimental Pharmacology for Natural Sciences, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, D-06120 Halle, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Hoppst\u00e4dter","sequence":"additional","affiliation":[{"name":"Pharmaceutical Biology, Department of Pharmacy, Saarland University, Campus C2.3, D-66123 Saarbr\u00fccken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7224-9900","authenticated-orcid":false,"given":"Alexandra K.","family":"Kiemer","sequence":"additional","affiliation":[{"name":"Pharmaceutical Biology, Department of Pharmacy, Saarland University, Campus C2.3, D-66123 Saarbr\u00fccken, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1016\/j.immuni.2021.03.005","article-title":"Longitudinal Profiling of Respiratory and Systemic Immune Responses Reveals Myeloid Cell-Driven Lung Inflammation in Severe COVID-19","volume":"54","author":"Szabo","year":"2021","journal-title":"Immunity"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"103086","DOI":"10.1016\/j.ebiom.2020.103086","article-title":"Blockade of an Innate Immune Amplifier to Fight Immune Hyperactivation in COVID-19?","volume":"61","author":"Kiemer","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"102836","DOI":"10.1016\/j.ebiom.2020.102836","article-title":"Targeting Innate Immunity by Blocking CD14: Novel Approach to Control Inflammation and Organ Dysfunction in COVID-19 Illness","volume":"57","author":"Martin","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"16018","DOI":"10.1038\/npjamd.2016.18","article-title":"Macrophages in Age-Related Chronic Inflammatory Diseases","volume":"2","author":"Oishi","year":"2016","journal-title":"NPJ Aging Mech. Dis."},{"key":"ref_5","first-page":"226","article-title":"Pneumonia in the Elderly (Geriatric) Population","volume":"11","author":"Janssens","year":"2005","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2974","DOI":"10.1093\/eurheartj\/ehz961","article-title":"Inflamm-Ageing: The Role of Inflammation in Age-Dependent Cardiovascular Disease","volume":"41","author":"Liberale","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/S0531-5565(02)00014-1","article-title":"Adipogenesis and Aging: Does Aging Make Fat Go MAD?","volume":"37","author":"Kirkland","year":"2002","journal-title":"Exp. Gerontol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e135197","DOI":"10.1172\/JCI135197","article-title":"TREM2 Sustains Macrophage-Hepatocyte Metabolic Coordination in Nonalcoholic Fatty Liver Disease and Sepsis","volume":"131","author":"Hou","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2748","DOI":"10.1007\/s00261-020-02648-7","article-title":"Higher Frequency of Hepatic Steatosis at CT among COVID-19-Positive Patients","volume":"45","author":"Medeiros","year":"2020","journal-title":"Abdom. Radiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"100057","DOI":"10.1016\/j.metop.2020.100057","article-title":"The Incidence of COVID-19 in Patients with Metabolic Syndrome and Non-Alcoholic Steatohepatitis: A Population-Based Study","volume":"8","author":"Ghoneim","year":"2020","journal-title":"Metabol. Open"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1578","DOI":"10.1097\/MEG.0000000000001902","article-title":"Nonalcoholic Fatty Liver Disease Is Associated with COVID-19 Severity Independently of Metabolic Syndrome: A Retrospective Case-Control Study","volume":"33","author":"Mahamid","year":"2021","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"636637","DOI":"10.3389\/fmed.2021.636637","article-title":"Hepatic Steatosis, Rather Than Underlying Obesity, Increases the Risk of Infection and Hospitalization for COVID-19","volume":"8","author":"Dennis","year":"2021","journal-title":"Front. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"770986","DOI":"10.3389\/fendo.2021.770986","article-title":"Endotoxins and Non-Alcoholic Fatty Liver Disease","volume":"12","author":"Kessoku","year":"2021","journal-title":"Front. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Nier, A., Huber, Y., Labenz, C., Michel, M., Bergheim, I., and Schattenberg, J.M. (2020). Adipokines and Endotoxemia Correlate with Hepatic Steatosis in Non-Alcoholic Fatty Liver Disease (NAFLD). Nutrients, 12.","DOI":"10.3390\/nu12030699"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1159\/000235677","article-title":"Non-Alcoholic Fatty Liver Disease in Older People","volume":"55","author":"Frith","year":"2009","journal-title":"Gerontology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/nyas.14333","article-title":"Myeloid Cells in Sepsis-Acquired Immunodeficiency","volume":"1499","author":"Venet","year":"2021","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1179\/096805104225003997","article-title":"Molecular Mechanism of Endotoxin Tolerance","volume":"10","author":"Fan","year":"2004","journal-title":"J. Endotoxin Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/jcb.27547","article-title":"Recent Advances in Endotoxin Tolerance","volume":"120","author":"Liu","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"38446","DOI":"10.18632\/oncotarget.6197","article-title":"Glucocorticoid-Induced Leucine Zipper (GILZ) in Immuno Suppression: Master Regulator or Bystander?","volume":"6","author":"Kiemer","year":"2015","journal-title":"Oncotarget"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6057","DOI":"10.4049\/jimmunol.1403207","article-title":"Glucocorticoid-Induced Leucine Zipper: A Critical Factor in Macrophage Endotoxin Tolerance","volume":"194","author":"Kessler","year":"2015","journal-title":"J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.it.2009.07.009","article-title":"Endotoxin Tolerance: New Mechanisms, Molecules and Clinical Significance","volume":"30","author":"Biswas","year":"2009","journal-title":"Trends Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.3389\/fimmu.2018.02705","article-title":"Regulation of Endotoxin Tolerance and Compensatory Anti-Inflammatory Response Syndrome by Non-Coding RNAs","volume":"9","author":"Vergadi","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ebiom.2014.10.003","article-title":"An Endotoxin Tolerance Signature Predicts Sepsis and Organ Dysfunction at Initial Clinical Presentation","volume":"1","author":"Pena","year":"2014","journal-title":"EBioMedicine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e13156","DOI":"10.1111\/acel.13156","article-title":"Altered Glucocorticoid Metabolism Represents a Feature of Macroph-Aging","volume":"19","author":"Linnenberger","year":"2020","journal-title":"Aging Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s00005-015-0377-3","article-title":"Inflammaging and Anti-Inflammaging: The Role of Cytokines in Extreme Longevity","volume":"64","author":"Minciullo","year":"2016","journal-title":"Arch. Immunol. Ther. Exp."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3005","DOI":"10.1210\/jc.2002-021687","article-title":"Interleukin-6 Stimulates Lipolysis and Fat Oxidation in Humans","volume":"88","author":"Steensberg","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s41597-020-00668-y","article-title":"Systematic Analysis of Infectious Disease Outcomes by Age Shows Lowest Severity in School-Age Children","volume":"7","author":"Glynn","year":"2020","journal-title":"Sci. Data"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5762","DOI":"10.3390\/ijms15045762","article-title":"Fatty Acid Elongation in Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma","volume":"15","author":"Kessler","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1002\/glia.20467","article-title":"Systemic LPS Causes Chronic Neuroinflammation and Progressive Neurodegeneration","volume":"55","author":"Qin","year":"2007","journal-title":"Glia"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6171","DOI":"10.1128\/AAC.01497-13","article-title":"Impact of Lipopolysaccharide-Induced Inflammation on the Disposition of the Aminocephalosporin Cefadroxil","volume":"57","author":"Huh","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1159\/000475931","article-title":"In Vivo Lipopolysaccharide Tolerance Recruits CD11b+ Macrophages to the Liver with Enhanced Bactericidal Activity and Low Tumor Necrosis Factor-Releasing Capability, Resulting in Drastic Resistance to Lethal Septicemia","volume":"9","author":"Kinoshita","year":"2017","journal-title":"J. Innate Immun."},{"key":"ref_32","first-page":"3845","article-title":"Endotoxin Tolerance Induced by Lipopolysaccharide Preconditioning Protects against Surgery-Induced Cognitive Impairment in Aging Mice","volume":"17","author":"Zhang","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1097\/SHK.0b013e3181aa9690","article-title":"Chronic Pulmonary LPS Tolerance Induces Selective Immunosuppression While Maintaining the Neutrophilic Response","volume":"33","author":"Natarajan","year":"2010","journal-title":"Shock"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1097\/CCM.0b013e31819c3c67","article-title":"Development of Endotoxin Tolerance in Humans in Vivo","volume":"37","author":"Draisma","year":"2009","journal-title":"Crit. Care Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1177\/1753425909105548","article-title":"Endotoxin Tolerance Does Not Limit Mild Ischemia-Reperfusion Injury in Humans In Vivo","volume":"15","author":"Draisma","year":"2009","journal-title":"Innate Immun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1016\/j.imbio.2017.01.003","article-title":"Hepatic Interleukin-6 Production Is Maintained during Endotoxin Tolerance and Facilitates Lipid Accumulation","volume":"222","author":"Dembek","year":"2017","journal-title":"Immunobiology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1161\/01.STR.0000143450.04438.ae","article-title":"Endotoxin Preconditioning Prevents Cellular Inflammatory Response during Ischemic Neuroprotection in Mice","volume":"35","author":"Rosenzweig","year":"2004","journal-title":"Stroke"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1038\/cdd.2014.212","article-title":"A Unique Role for P53 in the Regulation of M2 Macrophage Polarization","volume":"22","author":"Li","year":"2015","journal-title":"Cell Death Differ."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4684","DOI":"10.1096\/fj.201902557RRR","article-title":"The Glucocorticoid-Induced Leucine Zipper Mediates Statin-Induced Muscle Damage","volume":"34","author":"Linnenberger","year":"2020","journal-title":"FASEB J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1080\/00401706.1964.10490181","article-title":"Multiple Comparisons Using Rank Sums","volume":"6","year":"1964","journal-title":"Technometrics"},{"key":"ref_41","first-page":"65","article-title":"A Simple Sequentially Rejective Multiple Test Procedure","volume":"6","author":"Holm","year":"1979","journal-title":"Scand. J. Stat."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kr\u00f6hler, T., Kessler, S.M., Hosseini, K., List, M., Barghash, A., Patial, S., Laggai, S., Gemperlein, K., Haybaeck, J., and M\u00fcller, R. (2019). The MRNA-Binding Protein TTP\/ZFP36 in Hepatocarcinogenesis and Hepatocellular Carcinoma. Cancers, 11.","DOI":"10.3390\/cancers11111754"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1002\/hep.25932","article-title":"Elovl6 Promotes Nonalcoholic Steatohepatitis","volume":"56","author":"Matsuzaka","year":"2012","journal-title":"Hepatology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1194\/jlr.M045500","article-title":"The IGF2 MRNA Binding Protein P62\/IGF2BP2-2 Induces Fatty Acid Elongation as a Critical Feature of Steatosis","volume":"55","author":"Laggai","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/febs.15061","article-title":"Regulation of Inflammation as an Anti-Aging Intervention","volume":"287","author":"Neves","year":"2020","journal-title":"FEBS J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.ypmed.2011.11.011","article-title":"Age-Associated Chronic Diseases Require Age-Old Medicine: Role of Chronic Inflammation","volume":"54","author":"Prasad","year":"2012","journal-title":"Prev. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"367","DOI":"10.14336\/AD.2018.0324","article-title":"Redefining Chronic Inflammation in Aging and Age-Related Diseases: Proposal of the Senoinflammation Concept","volume":"10","author":"Chung","year":"2019","journal-title":"Aging Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"162","DOI":"10.4049\/jimmunol.2001449","article-title":"SARS-CoV-2 Proteins Induce Endotoxin Tolerance Hallmarks: A Demonstration in Patients with COVID-19","volume":"207","year":"2021","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e140329","DOI":"10.1172\/jci.insight.140329","article-title":"Severe Immunosuppression and Not a Cytokine Storm Characterizes COVID-19 Infections","volume":"5","author":"Remy","year":"2020","journal-title":"JCI Insight"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Kruglikov, I.L., and Scherer, P.E. (2021). Preexisting and Inducible Endotoxemia as Crucial Contributors to the Severity of COVID-19 Outcomes. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009306"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.bbi.2009.12.004","article-title":"Differential Sensitivity to Endotoxin Exposure in Young and Middle-Age Mice","volume":"24","author":"Kohman","year":"2010","journal-title":"Brain Behav. Immun."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Sun, Y., Li, H., Yang, M.F., Shu, W., Sun, M.J., and Xu, Y. (2012). Effects of Aging on Endotoxin Tolerance Induced by Lipopolysaccharides Derived from Porphyromonas Gingivalis and Escherichia Coli. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0039224"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/0005-2760(81)90252-6","article-title":"Effects of Temperature Acclimation on Neurospora Phospholipids. Fatty Acid Desaturation Appears to Be a Key Element in Modifying Phospholipid Fluid Properties","volume":"665","author":"Martin","year":"1981","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s13340-020-00481-3","article-title":"Role of Fatty Acid Elongase Elovl6 in the Regulation of Energy Metabolism and Pathophysiological Significance in Diabetes","volume":"12","author":"Matsuzaka","year":"2021","journal-title":"Diabetol. Int."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/acel.12416","article-title":"Age-Associated Changes in Long-Chain Fatty Acid Profile during Healthy Aging Promote pro-Inflammatory Monocyte Polarization via PPAR\u03b3","volume":"15","author":"Pararasa","year":"2016","journal-title":"Aging Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1007\/s00281-019-00747-2","article-title":"The Role of Interleukin-6 in Glucose Homeostasis and Lipid Metabolism","volume":"41","author":"Lehrskov","year":"2019","journal-title":"Semin. Immunopathol."},{"key":"ref_57","first-page":"347","article-title":"Reduction in the Stearic to Oleic Acid Ratio in Human Malignant Liver Neoplasms","volume":"11","author":"Wood","year":"1985","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1002\/hep.23229","article-title":"The Plasma Lipidomic Signature of Nonalcoholic Steatohepatitis","volume":"50","author":"Puri","year":"2009","journal-title":"Hepatology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1186\/s12944-020-01346-z","article-title":"A High Fat Diet with a High C18:0\/C16:0 Ratio Induced Worse Metabolic and Transcriptomic Profiles in C57BL\/6 Mice","volume":"19","author":"Wang","year":"2020","journal-title":"Lipids Health Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1111\/liv.12685","article-title":"Characteristics of Hepatic Fatty Acid Compositions in Patients with Nonalcoholic Steatohepatitis","volume":"35","author":"Yamada","year":"2015","journal-title":"Liver Int."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/12\/4\/530\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:07:51Z","timestamp":1760123271000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/12\/4\/530"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,31]]},"references-count":60,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["biology12040530"],"URL":"https:\/\/doi.org\/10.3390\/biology12040530","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,31]]}}}