{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T14:14:13Z","timestamp":1793369653419,"version":"4.5.0"},"reference-count":111,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T00:00:00Z","timestamp":1651795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, Cluj\u2013Napoca","award":["5200\/74\/1.03.2017"],"award-info":[{"award-number":["5200\/74\/1.03.2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Nonalcoholic fatty liver disease (NAFLD) is a new challenge in modern medicine, due to its high prevalence in the world. The pathogenesis of NAFLD is a complex dysmetabolic process, following the \u201cmultiple-hit\u201d hypothesis that involves hepatocytes excessive accumulation of triglycerides, insulin resistance (IR), increased oxidative stress, chronic low-grade inflammatory response and lipotoxicity. In this review, we provide an overview of the interrelation of these processes, the link between systemic and local inflammation and the role of dysfunctional adipose tissue (AT) in the NAFLD development. Multiple extrahepatic triggers of the pathophysiological mechanisms of NAFLD are described: nutritional deficiency or malnutrition, unhealthy food intake, the dysfunction of the liver\u2013gut axis, the involvement of the mesenteric adipose tissue, the role of adipokines such as adiponectin, of food intake hormone, the leptin and leptin resistance (LR) and adipose tissue\u2019s hormone, the resistin. In addition, a wide range of intrahepatic players are involved: oxidative stress, fatty acid oxidation, endoplasmic reticulum stress, mitochondrial dysfunction, resident macrophages (Kupffer cells), neutrophils, dendritic cells (DCs), B and T lymphocytes contributing to the potential evolution of NAFLD to nonalcoholic steatohepatitis (NASH). This interdependent approach to complex dysmetabolic imbalance in NAFLD, integrating relevant studies, could contribute to a better clarification of pathogenesis and consequently the development of new personalized treatments, targeting de novo lipogenesis, chronic inflammation and fibrosis. Further studies are needed to focus not only on treatment, but also on prevention strategy in NAFLD.<\/jats:p>","DOI":"10.3390\/medicina58050641","type":"journal-article","created":{"date-parts":[[2022,5,8]],"date-time":"2022-05-08T21:31:20Z","timestamp":1652045480000},"page":"641","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":136,"title":["Chronic Inflammation\u2014A Link between Nonalcoholic Fatty Liver Disease (NAFLD) and Dysfunctional Adipose Tissue"],"prefix":"10.3390","volume":"58","author":[{"given":"Maria","family":"Petrescu","sequence":"first","affiliation":[{"name":"Department of Community Medicine, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia Irina","family":"Vlaicu","sequence":"additional","affiliation":[{"name":"5th Department\u2013Internal Medicine, 1st Medical Clinic, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Cium\u0103rnean","sequence":"additional","affiliation":[{"name":"5th Department\u2013Internal Medicine, 4th Medical Clinic, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5087-9282","authenticated-orcid":false,"given":"Mircea Vasile","family":"Milaciu","sequence":"additional","affiliation":[{"name":"5th Department\u2013Internal Medicine, 4th Medical Clinic, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Codru\u021ba","family":"M\u0103rginean","sequence":"additional","affiliation":[{"name":"Department of Community Medicine, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Florea","sequence":"additional","affiliation":[{"name":"Department of Community Medicine, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4549-3526","authenticated-orcid":false,"given":"\u0218tefan Cristian","family":"Vesa","sequence":"additional","affiliation":[{"name":"2nd Department\u2013Functional Sciences, Discipline of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Popa","sequence":"additional","affiliation":[{"name":"Department of Community Medicine, Faculty of Medicine, \u201cIuliu Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.freeradbiomed.2018.06.015","article-title":"B2-lymphocyte responses to oxidative stress-derived antigens contribute to the evolution of nonalcoholic fatty liver disease (NAFLD)","volume":"124","author":"Sutti","year":"2018","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1002\/hep.24001","article-title":"Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis","volume":"52","author":"Tilg","year":"2010","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature10809","article-title":"Inflammasome-mediated dysbiosis regultes progression of NAFLD and obesity","volume":"482","author":"Elinav","year":"2012","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.trsl.2020.11.003","article-title":"Nonalcoholic fatty liver disease (NAFLD) severity is associated to a nonhemostatic contribution an proinflammatory phenotype of platelets","volume":"231","author":"Miele","year":"2021","journal-title":"Transl. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"24399","DOI":"10.1038\/srep24399","article-title":"A pharmacological inhibitor of NLRP3 inflammasome prevents non-alcoholic fatty liver disease in a mouse model induced by high fat diet","volume":"6","author":"Yang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wehr, A., Baeck, C., Ulmer, F., Gassler, N., Hittatiya, K., Luedde, T., Neumann, U.P., Trautwein, C., and Tacke, F. (2014). Pharmacological inhibition of the chemokine CXCL16 diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112327"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e13076","DOI":"10.1111\/jfbc.13076","article-title":"Zingiber officinale extract and omega-3 fatty acids ameliorate endoplasmic reticulum stress in a nonalcoholic fatty liver rat model","volume":"43","author":"Kandeil","year":"2019","journal-title":"J. Food Biochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.bbalip.2011.10.016","article-title":"Roles of PPARs in NAFLD: Potential therapeutic targets","volume":"1821","author":"Tailleux","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1053\/j.gastro.2019.12.054","article-title":"Adipose Tissue-Liver Cross Talk in the Control of Whole-Body Metabolism: Implications in Nonalcoholic Fatty Liver Disease","volume":"158","author":"Azzu","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/s41575-018-0009-6","article-title":"Triggering and resolution of inflammation in NASH","volume":"15","author":"Schuster","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1007\/s10620-016-4095-4","article-title":"Natural History of Nonalcoholic Fatty Liver Disease","volume":"61","author":"Goh","year":"2016","journal-title":"Dig. Dis. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S47","DOI":"10.1016\/j.jhep.2014.12.012","article-title":"NAFLD: A multisystem disease","volume":"62","author":"Byrne","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/hep4.1799","article-title":"Direct AMPK Activation Corrects NASH in Rodents Through Metabolic Effects and Direct Action on Inflammation and Fibrogenesis","volume":"6","author":"Foretz","year":"2022","journal-title":"Hepatol. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1002\/hep.26717","article-title":"Extra-hepatic complications of nonalcoholic fatty liver disease","volume":"59","author":"Armstrong","year":"2014","journal-title":"Hepatology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.cld.2015.10.010","article-title":"Progression and Natural History of Nonalcoholic Fatty Liver Disease in Adults","volume":"20","author":"Marengo","year":"2016","journal-title":"Clin. Liver Dis."},{"key":"ref_17","first-page":"256","article-title":"High-fat diet induced obesity primes inflammation in adipose tissue prior to liver in C57BL\/6j mice","volume":"7","author":"Sheedfar","year":"2015","journal-title":"Aging (Albany NY)"},{"key":"ref_18","first-page":"2683","article-title":"Morphological and functional characterization of non-alcoholic fatty liver disease induced by a methionine-choline-deficient diet in C57BL\/6 mice","volume":"6","author":"Itagaki","year":"2013","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e1900385","DOI":"10.1002\/mnfr.201900385","article-title":"Industrial Trans Fatty Acids Stimulate SREBP2-Mediated Cholesterogenesis and Promote Non-Alcoholic Fatty Liver Disease","volume":"63","author":"Oteng","year":"2019","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1055\/s-0032-1321819","article-title":"Reversion of steatosis by SREBP-1c antisense oligonucleotide did not improve hepatic insulin action in diet-induced obesity mice","volume":"44","author":"Vitto","year":"2012","journal-title":"Horm. Metab. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.2337\/db06-0200","article-title":"Liver-specific inhibit of ChREBP improves hepatic steatosis and insulin resistance in ob\/ob mice","volume":"55","author":"Dentin","year":"2006","journal-title":"Diabetes"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1172\/JCI41636","article-title":"The lipogenic transcription factor ChREBP dissociates hepatic steatosis from insulin resistance in mice and humans","volume":"122","author":"Benhamed","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_23","first-page":"14","article-title":"A critical role for ChREBP-mediated FGF21 secretion in hepatic fructose metabolism","volume":"6","author":"Kim","year":"2016","journal-title":"Mol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e96703","DOI":"10.1172\/jci.insight.96703","article-title":"Intestinal, but not hepatic, ChREBP is required for fructose tolerance","volume":"2","author":"Kim","year":"2017","journal-title":"JCI Insight"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"s13020","DOI":"10.1186\/s13020-015-0054-9","article-title":"Crude triterpenoid saponins from Ilex latifolia (Da Ye Dong Qing) ameliorate lipid accumulation by inhibiting SREBP expression via activation of AMPK in a non-alcoholic fatty liver disease model","volume":"10","author":"Feng","year":"2015","journal-title":"Chin. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5246725","DOI":"10.1155\/2020\/5246725","article-title":"Anti-inflammatory Mechanism of Ruzu Bitters on Diet-Induced Nonalcoholic Fatty Liver Disease in Male Wistar Rats","volume":"2020","author":"Ogunlana","year":"2020","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"173314","DOI":"10.1016\/j.ejphar.2020.173314","article-title":"Magnesium isoglycyrrhizinate alleviates fructose-induced liver oxidative stress and inflammatory injury through suppressing NOXs","volume":"883","author":"Yang","year":"2020","journal-title":"Eur. J. Pharm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3760","DOI":"10.1111\/bph.15099","article-title":"Astaxanthin attenuates hepatic damage and mitochondrial dysfunction in non-alcoholic fatty liver disease by up-regulating the FGF21\/PGC-1\u03b1 pathway","volume":"177","author":"Wu","year":"2020","journal-title":"Br. J. Pharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"101","DOI":"10.4161\/21623945.2014.978662","article-title":"The role of visceral and subcutaneous adipose tissue fatty acid composition in liver pathophysiology associated with NAFLD","volume":"4","author":"Gentile","year":"2015","journal-title":"Adipocyte"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"44612","DOI":"10.1038\/srep44612","article-title":"Effect of modulation of PPAR-\u03b3 activity on Kupffer cells M1\/M2 polarization in the development of non-alcoholic fatty liver disease","volume":"7","author":"Luo","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Federico, A., Dallio, M., Caprio, G.G., Gravina, A.G., Picascia, D., Masarone, M., Persico, M., and Loguercio, C. (2017). Qualitative and quantitative evaluation of dietary intake in patients with non-alcoholic steatohepatitis. Nutrients, 9.","DOI":"10.3390\/nu9101074"},{"key":"ref_32","first-page":"G336","article-title":"Investigating fibrosis and inflammation in an ex vivo NASH murine model","volume":"318","author":"Gore","year":"2020","journal-title":"Am. J. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Rafiei, H., Omidian, K., and Bandy, B. (2019). Dietary polyphenols protect against oleic acid-induced steatosis in an in vitro model of NAFLD by modulating lipid metabolism and improving mitochondrial function. Nutrients, 11.","DOI":"10.3390\/nu11030541"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/j.jfda.2018.01.005","article-title":"Tetrahydrocurcumin ameliorates free fatty acid-induced hepatic steatosis and improves insulin resistance in HepG2 cells","volume":"26","author":"Chen","year":"2018","journal-title":"J. Food Drug Anal."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"607","DOI":"10.14309\/ajg.0000000000000154","article-title":"Angiotensin II Type 1 Receptor rs5186 Gene Variant Predicts Incident NAFLD and Associated Hypertension: Role of Dietary Fat-Induced Pro-Inflammatory Cell Activation","volume":"114","author":"Musso","year":"2019","journal-title":"Am. J. Gastroenterol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Shih, P.H., Shiue, S.J., Chen, C.N., Cheng, S.W., Lin, H.Y., Wu, L.W., and Wu, M.-S. (2021). Fucoidan and fucoxanthin attenuate hepatic steatosis and inflammation of NAFLD through modulation of leptin\/adiponectin axis. Mar. Drugs, 19.","DOI":"10.3390\/md19030148"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Chyau, C.C., Wang, H.F., Zhang, W.J., Chen, C.C., Huang, S.H., Chang, C.C., and Peng, R.Y. (2020). Antrodan alleviates high-fat and high-fructose diet-induced fatty liver disease in C57BL\/6 mice model via AMPK\/Sirt1\/SREBP-1c\/PPAR\u03b3 pathway. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21010360"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"10878","DOI":"10.1021\/acsomega.0c00529","article-title":"Ginsenoside Rg1 Regulates Liver Lipid Factor Metabolism in NAFLD Model Rats","volume":"5","author":"Hou","year":"2020","journal-title":"ACS Omega"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"622841","DOI":"10.3389\/fphar.2021.622841","article-title":"Ginsenosides Improve Nonalcoholic Fatty Liver Disease via Integrated Regulation of Gut Microbiota, Inflammation and Energy Homeostasis","volume":"12","author":"Liang","year":"2021","journal-title":"Front. Pharm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"153388","DOI":"10.1016\/j.phymed.2020.153388","article-title":"Modulation of IR as a therapeutic target to prevent NASH using NRF from Diceratella elliptica (DC.) jonsell. Strong Nrf2 and leptin inducer as well as NF-kB inhibitor","volume":"80","author":"Mohammed","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Sangineto, M., Bukke, V.N., Bellanti, F., Tamborra, R., Moola, A., Duda, L., Villani, R., Romano, A.D., and Serviddio, G. (2021). A novel nutraceuticals mixture improves liver steatosis by preventing oxidative stress and mitochondrial dysfunction in a nafld model. Nutrients, 13.","DOI":"10.3390\/nu13020652"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"109895","DOI":"10.1016\/j.biopha.2020.109895","article-title":"Scoparone improves hepatic inflammation and autophagy in mice with nonalcoholic steatohepatitis by regulating the ROS\/P38\/Nrf2 axis and PI3K\/AKT\/mTOR pathway in macrophages","volume":"125","author":"Liu","year":"2020","journal-title":"Biomed. Pharm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"105797","DOI":"10.1016\/j.intimp.2019.105797","article-title":"Scoparone alleviates inflammation, apoptosis an fibrosis of non-alcoholic steatohepatitis by supressing the TLR4\/NF-\u03baB signaling pathway mice","volume":"75","author":"Liu","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1111\/bph.14938","article-title":"Naringenin attenuates non-alcoholic fatty liver disease by down-regulating the NLRP3\/NF-\u03baB pathway in mice","volume":"177","author":"Wang","year":"2020","journal-title":"Br. J. Pharm."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.redox.2018.07.002","article-title":"Polydatin prevents fructose-induced liver inflammation and lipid deposition through increasing miR-200a to regulate Keap1\/Nrf2 pathway","volume":"18","author":"Zhao","year":"2018","journal-title":"Redox. Biol."},{"key":"ref_46","first-page":"1191","article-title":"The role of acylated ghrelin and unacylated ghrelin in the blood and hypothalamus and their interaction with nonalcoholic fatty liver disease","volume":"23","author":"Liu","year":"2020","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1016\/j.cmet.2020.08.001","article-title":"A Membrane-Bound Diacylglycerol species induces PKC-mediated hepatic insulin resistance","volume":"32","author":"Lyu","year":"2020","journal-title":"Cell Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2200","DOI":"10.3389\/fmicb.2018.02200","article-title":"Beef, casein, and soy Proteins differentially affect lipid metabolism, triglycerides accumulation and gut microbiota of high-fat-diet-fed C57BL\/6J mice","volume":"9","author":"Ijaz","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.cmet.2005.06.006","article-title":"Prevention of hepatic steatosis and hepatic insulin resistance in mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 knockout mice","volume":"2","author":"Neschen","year":"2005","journal-title":"Cell Metab."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.diabet.2019.01.005","article-title":"Insulin resistance and NAFLD: Relationship with intrahepatic iron and serum TNF-\u03b1 using 1H MR spectroscopy and MRI","volume":"45","year":"2019","journal-title":"Diabetes Metab."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1097\/MEG.0b013e32835609b0","article-title":"How adiponectin, leptin, and ghrelin orchestrate together and correlate with the severity of nonalcoholic fatty liver disease","volume":"24","author":"MacHado","year":"2012","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2888","DOI":"10.3748\/wjg.14.2888","article-title":"Serum leptin and soluble leptin receptor in non-alcoholic fatty liver disease","volume":"14","author":"Huang","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"197","DOI":"10.3892\/etm.2020.9327","article-title":"Interactions between leptin and insulin resistance in patients with prediabetes, with and without NAFLD","volume":"20","author":"Bungau","year":"2020","journal-title":"Exp. Med."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Hossain, I.A., Akter, S., Rahman, M.K., and Ali, L. (2015). Gender specific association of serum leptin and insulinemic indices with nonalcoholic fatty liver disease in prediabetic subjects. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0142165"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1053\/jhep.2001.26518","article-title":"Leptin augments inflammatory and profibrogenic responses in the murine liver induced by hepatotoxic chemicals","volume":"34","author":"Ikejima","year":"2001","journal-title":"Hepatology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.dld.2010.04.005","article-title":"Relationship between white blood cell count and nonalcoholic fatty liver disease","volume":"42","author":"Lee","year":"2010","journal-title":"Dig. Liver Dis."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"G659","DOI":"10.1152\/ajpgi.00079.2018","article-title":"Mesenteric adipose tissue contributes to intestinal barrier integrity and protects against nonalcoholic fatty liver disease in mice","volume":"315","author":"Wu","year":"2018","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1055\/a-1293-8250","article-title":"Acute Elevated Resistin Exacerbates Mitochondrial Damage and Aggravates Liver Steatosis through AMPK\/PGC-1\u03b1 Signaling Pathway in Male NAFLD Mice","volume":"53","author":"Wen","year":"2021","journal-title":"Horm. Metab. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4021623","DOI":"10.1155\/2019\/4021623","article-title":"Visfatin Induces Inflammation and Insulin Resistance via the NF-\u03baB and STAT3 Signaling Pathways in Hepatocytes","volume":"2019","author":"Heo","year":"2019","journal-title":"J. Diabetes Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1055\/a-0897-8565","article-title":"Association Between Visfatin and Hepatic Steatosis in the General Population During Long-Term Follow-Up","volume":"51","author":"Johannsen","year":"2019","journal-title":"Horm. Metab. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/S1665-2681(19)31338-9","article-title":"Association of plasma visfatin with hepatic and systemic inflammation in nonalcoholic fatty liver disease","volume":"12","author":"Genc","year":"2013","journal-title":"Ann. Hepatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.cell.2014.06.005","article-title":"Adipsin is an Adipokine that Improves \u03b2 Cell Function in Diabetes","volume":"158","author":"Lo","year":"2014","journal-title":"Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1159\/000520368","article-title":"Inverse Association of Serum Adipsin with the Remission of Nonalcoholic Fatty-Liver Disease: A 3-Year Community-Based Cohort Study","volume":"78","author":"Gu","year":"2022","journal-title":"Ann. Nutr. Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1159\/000495215","article-title":"Association of circulating adipsin, visfatin, and adiponectine with nonalcoholic fatty liver disease in adults: A case-control study","volume":"74","author":"Qiu","year":"2019","journal-title":"Ann. Nutr. Metab."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3109\/00365521.2010.516452","article-title":"Serum levels of omentin, chemerin and adipsin in patients with biopsy-proven nonalcoholic fatty liver disease","volume":"46","author":"Yilmaz","year":"2011","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1016\/j.biopha.2018.04.143","article-title":"Dihydrocurcumin ameliorates the lipid accumulation, oxidative stress and insulin resistance in oleic acid-induced L02 and HepaG2 cells","volume":"103","author":"Yu","year":"2018","journal-title":"Biomed. Pharm."},{"key":"ref_67","first-page":"277","article-title":"Omentin, Vaspin and irisin in chronic liver disease","volume":"70","author":"Waluga","year":"2019","journal-title":"J. Physiol. Pharm."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"470","DOI":"10.2478\/jomb-2018-0006","article-title":"Are Vaspin and Omentin-1 Related to Insulin Resistance, Blood Pressure and Inflammation in NAFLD Patients?","volume":"37","author":"Aliasghari","year":"2018","journal-title":"J. Med. Biochem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.metabol.2010.05.008","article-title":"Serum levels of vaspin, obestatin, and apelin-36 in patients with nonalcoholic fatty liver disease","volume":"60","author":"Aktas","year":"2011","journal-title":"Metabolism"},{"key":"ref_70","first-page":"607","article-title":"Visfatin\/PBEF\/Nampt induced EMMPRIN and MMP-9 production in macrophages via the NAMPT-MAPK (p38, ERK1\/2)-NF-\u03baB signaling pathway","volume":"27","author":"Fan","year":"2011","journal-title":"Int. J. Mol. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.hepres.2005.09.020","article-title":"Clinicopathological significance of oxidative cellular damage in non-alcoholic fatty liver diseases","volume":"33","author":"Seki","year":"2005","journal-title":"Hepatol. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4192","DOI":"10.7150\/thno.21400","article-title":"Pro-inflammatory CXCR3 impairs mitochondrial function in experimental non-alcoholic steatohepatitis","volume":"7","author":"Du","year":"2017","journal-title":"Theranostics"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.jhep.2017.01.022","article-title":"NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice","volume":"66","author":"Mridha","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"112801","DOI":"10.1016\/j.yexcr.2021.112801","article-title":"MIG\/CXCL9 exacerbates the progression of metabolic-associated fatty liver disease by disrupting Treg\/Th17 balance","volume":"407","author":"Li","year":"2021","journal-title":"Exp. Cell Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.1002\/jcb.25973","article-title":"Mixed lineage kinase 3 mediates the induction of CXCL10 by a STAT1-dependent mechanism during hepatocyte lipotoxicity","volume":"118","author":"Tomita","year":"2017","journal-title":"J. Cell Biochem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.7150\/thno.19068","article-title":"C-X-C motif chemokine 10 impairs autophagy and autolysosome formation in non-alcoholic steatohepatitis","volume":"7","author":"Zhang","year":"2017","journal-title":"Theranostics"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1007\/s00535-019-01565-x","article-title":"Noninvasive diagnostic criteria for nonalcoholic steatohepatitis based on gene expression levels in peripheral blood mononuclear cells","volume":"54","author":"Kado","year":"2019","journal-title":"J. Gastroenterol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5226","DOI":"10.4049\/jimmunol.1202909","article-title":"Chemokine Receptor CXCR6-Dependent Hepatic NK T Cell Accumulation Promotes Inflammation and Liver Fibrosis","volume":"190","author":"Wehr","year":"2013","journal-title":"J. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"8435178","DOI":"10.1155\/2017\/8435178","article-title":"Shorter Leukocyte Telomere Length in Relation to Presumed Nonalcoholic Fatty Liver Disease in Mexican-American Men in NHANES 1999\u20132002","volume":"2017","author":"Wojcicki","year":"2017","journal-title":"Int. J. Hepatol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e010342","DOI":"10.1136\/bmjopen-2015-010342","article-title":"Association between white blood cell count and non-alcoholic fatty liver disease in urban Han Chinese: A prospective cohort study","volume":"6","author":"Wang","year":"2016","journal-title":"BMJ Open"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.1038\/s41467-020-16991-2","article-title":"Silencing hepatic MCJ attenuates non-alcoholic fatty liver disease (NAFLD) by increasing mitochondrial fatty acid oxidation","volume":"11","author":"Fortner","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1016\/j.cmet.2020.10.010","article-title":"TANK-Binding Kinase 1 Regulate the Localization of Acyl-CoA Synthase ACSL1 to Control Hepatic Fatty Acid Oxidation","volume":"32","author":"Huh","year":"2020","journal-title":"Cell Metab."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.taap.2019.01.003","article-title":"Farnesol induces fatty acid oxidation and decreases triglyceride accumulation in steatotic HepaRG cells","volume":"365","author":"Pant","year":"2019","journal-title":"Toxicol. Appl. Pharm."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1007\/s10753-020-01190-4","article-title":"Mice Deficient in the IL-1\u03b2 Activation Genes Prtn3, Elane and Casp1 Are Protected Against the Development of Obesity-Induced NAFLD","volume":"43","author":"Mirea","year":"2020","journal-title":"Inflammation"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e431","DOI":"10.1038\/emm.2017.243","article-title":"PIK3R3 regulates PPAR\u03b1 expression to stimulate fatty acid \u03b2-oxidation and decrease hepatosteatosis","volume":"50","author":"Yang","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.jhep.2016.11.020","article-title":"PARP1-mediates PPAR\u03b1 poly(ADP-ribosyl)ation supresses fatty acid oxidaion in non-alcoholic fatty liver disease","volume":"66","author":"Huang","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1042\/BCJ20180517","article-title":"ZNF300 stimulates fatty acid oxidation and alleviates hepatosteatosis through regulating PPAR\u03b1","volume":"476","author":"Yan","year":"2019","journal-title":"Biochem. J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1002\/hep.26698","article-title":"Transforming growth factor beta signaling in hepatocytes participates in steatohepatitis through regulation of cell death and lipid metabolism in mice","volume":"59","author":"Yang","year":"2014","journal-title":"Hepatology"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.jhep.2021.01.042","article-title":"FOXA3 induction under endoplasmic reticulum stress contributes to non-alcoholic fatty liver disease","volume":"75","author":"Liu","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1007\/s00018-019-03263-6","article-title":"Lipophagy mediated carbohydrate-induced changes of lipid metabolism via oxidative stress, endoplasmic reticulum (ER) stress and ChREBP\/PPAR\u03b3 pathways","volume":"77","author":"Zhao","year":"2020","journal-title":"Cell Mol. Life Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1089\/jmf.2018.4186","article-title":"Strontium alleviates endoplasmic reticulum stress in a nonalcoholic fatty liver disease model","volume":"21","author":"Jiang","year":"2018","journal-title":"J. Med. Food"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.mito.2020.12.010","article-title":"Mitochondrial dysfunction as a mechanistic biomarker in patients with non-alcoholic fatty liver disease (NAFLD)","volume":"57","author":"Ajaz","year":"2021","journal-title":"Mitochondrion"},{"key":"ref_93","first-page":"102","article-title":"Effects of lipids on mitochondrial functions","volume":"1862","author":"Doan","year":"2017","journal-title":"Biochem. Biophys. Acta\u2013Mol. Cell Biol. Lipids"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"14477","DOI":"10.1038\/ncomms14477","article-title":"Mitochondrial ATP transporter depletion protects mice against liver steatosis and insulin resistance","volume":"8","author":"Cho","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"3320","DOI":"10.1038\/s41467-021-23601-2","article-title":"Perilipin 5 links mitochondrial uncoupled respiration in brown fat to healthy white remodeling and systemic glucose tolerance","volume":"12","author":"Yang","year":"2021","journal-title":"Nat. Comun."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1002\/2211-5463.13146","article-title":"The role of SAMM50 in nonalcoholic fatty liver disease: From genetics to mechanisms","volume":"11","author":"Li","year":"2021","journal-title":"FEBS Open Bio."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"960","DOI":"10.3109\/09637486.2014.940285","article-title":"Mulberry leaf phenolics ameliorate hyperglycemia-induced oxidative stress and stabilize mitochondrial membrane potential in HepG2 cells","volume":"65","author":"Zou","year":"2014","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.jhep.2009.11.030","article-title":"Mitochondrial dysfunction precedes insulin resistance and hepatic steatosis and contributes to the natural history of non-alcoholic fatty liver disease in an obese rodent model","volume":"52","author":"Rector","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1007\/s12020-017-1323-4","article-title":"Neutrophil depletion improves diet-induced non-alcoholic fatty liver disease in mice","volume":"57","author":"Ou","year":"2017","journal-title":"Endocrine"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/ijo.2015.226","article-title":"Surgical removal of inflamed epididymal white adipose tissue attenuates the development of non-alcoholic steatohepatitis in obesity","volume":"40","author":"Mulder","year":"2016","journal-title":"Int. J. Obes. (Lond)"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"509","DOI":"10.47162\/RJME.62.2.17","article-title":"Systemic and adipose tissue inflammation in NASH: Correlations with histopathological aspects","volume":"62","author":"Micu","year":"2021","journal-title":"Rom. J. Morphol. Embryol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1080\/21623945.2021.1982164","article-title":"Association of cell death mechanisms and fibrosis in visceral white adipose tissue with pathological alteraions in the liver of morbidly obese patients with NAFLD","volume":"10","author":"Leven","year":"2021","journal-title":"Adipocyte"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.cellimm.2019.01.005","article-title":"Mesenteric lymph node CD4+ T lymphocytes migrate to liver and contribute to non-alcoholic fatty liver disease","volume":"337","author":"Su","year":"2019","journal-title":"Cell Immunol."},{"key":"ref_104","first-page":"2783","article-title":"Ablation of systemic SIRT1 activity promotes nonalcoholic fatty liver disease by affecting liver-mesenteric adipose tissue fatty acid mobilization","volume":"1863","author":"Cheng","year":"2017","journal-title":"Biochem. Biophys. Acta-Mol. Basis Dis."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e1700738","DOI":"10.1002\/mnfr.201700738","article-title":"Tomato Powder Inhibits Hepatic Steatosis and Inflammation Potentially Through Restoring SIRT1 Activity and Adiponectin Function Independent of Carotenoid Cleavage Enzymes in Mice","volume":"62","author":"Li","year":"2018","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1002\/hep.31822","article-title":"Increased adipose tissue fibrogenesis, not impaired expandability, is associated with nonalcoholic fatty liver disease","volume":"74","author":"Beals","year":"2021","journal-title":"Hepatology"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1016\/j.jcmgh.2021.07.008","article-title":"White adipose tissue autophagy and adipose-liver crosstalk exacerbate nonalcoholic fatty liver disease in mice","volume":"12","author":"Sakane","year":"2021","journal-title":"Cel. Mol. Gastroenterol. Hepatol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"157","DOI":"10.5625\/lar.2017.33.2.157","article-title":"Comparative study of fatty liver induced by methionine and choline-deficiency in C57BL\/6N mice originating from three different sources","volume":"33","author":"Kim","year":"2017","journal-title":"Lab. Anim. Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s13105-018-0654-9","article-title":"Lipid metabolism in adipose tissue and liver from diet-induced obese rats: A comparison between Wistar and Sprague-Dawley strains","volume":"74","author":"Miranda","year":"2018","journal-title":"J. Physiol. Biochem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"E418","DOI":"10.1152\/ajpendo.00319.2015","article-title":"Metabolic phenotype and adipose and liver features in a high-fat western diet-induced mouse model of obesity-linked NAFLD","volume":"310","author":"Luo","year":"2016","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_111","first-page":"304","article-title":"Liver fibrosis associated with adipose tissue and liver inflammation in an obesity model","volume":"76","author":"Setyaningsih","year":"2021","journal-title":"Med. J. Malays."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/5\/641\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:06:49Z","timestamp":1760137609000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/5\/641"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,6]]},"references-count":111,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["medicina58050641"],"URL":"https:\/\/doi.org\/10.3390\/medicina58050641","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,6]]}}}