{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T14:34:46Z","timestamp":1792074886233,"version":"4.4.0"},"reference-count":89,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T00:00:00Z","timestamp":1567900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010665","name":"H2020 Marie Sk\u0142odowska-Curie Actions","doi-asserted-by":"publisher","award":["721236"],"award-info":[{"award-number":["721236"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"publisher","award":["SAF2015-63904-R"],"award-info":[{"award-number":["SAF2015-63904-R"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Melatonin, an indole produced by pineal and extrapineal tissues, but also taken with a vegetarian diet, has strong anti-oxidant, anti-inflammatory and anti-obesogenic potentials. Non-alcoholic fatty liver disease (NAFLD) is the hepatic side of the metabolic syndrome. NAFLD is a still reversible phase but may evolve into steatohepatitis (NASH), cirrhosis and carcinoma. Currently, an effective therapy for blocking NAFLD staging is lacking. Silent information regulator 1 (SIRT1), a NAD+ dependent histone deacetylase, modulates the energetic metabolism in the liver. Micro-RNA-34a-5p, a direct inhibitor of SIRT1, is an emerging indicator of NAFLD grading. Thus, here we analyzed the effects of oral melatonin against NAFLD and underlying molecular mechanisms, focusing on steatosis, ER stress, mitochondrial shape and autophagy. Male C57BL\/6J (WT) and SIRT1 heterozygous (HET) mice were placed either on a high-fat diet (58.4% energy from lard) (HFD) or on a standard maintenance diet (8.4% energy from lipids) for 16 weeks, drinking melatonin (10 mg\/kg) or not. Indirect calorimetry, glucose tolerance, steatosis, inflammation, ER stress, mitochondrial changes, autophagy and microRNA-34a-5p expression were estimated. Melatonin improved hepatic metabolism and steatosis, influenced ER stress and mitochondrial shape, and promoted autophagy in WT HFD mice. Conversely, melatonin was ineffective in HET HFD mice, maintaining NASH changes. Indeed, autophagy was inconsistent in HET HFD or starved mice, as indicated by LC3II\/LC3I ratio, p62\/SQSTM1 and autophagosomes estimation. The beneficial role of melatonin in dietary induced NAFLD\/NASH in mice was related to reduced expression of microRNA-34a-5p and sterol regulatory element-binding protein (SREBP1) but only in the presence of full SIRT1 availability.<\/jats:p>","DOI":"10.3390\/cells8091053","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T04:12:40Z","timestamp":1568002360000},"page":"1053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":77,"title":["Melatonin Effects on Non-Alcoholic Fatty Liver Disease Are Related to MicroRNA-34a-5p\/Sirt1 Axis and Autophagy"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6767-6617","authenticated-orcid":false,"given":"Alessandra","family":"Stacchiotti","sequence":"first","affiliation":[{"name":"Division of Anatomy and Physiopathology, Department of Clinical and Experimental Sciences, University of Brescia, Viale Europa 11, 25123 Brescia, Italy"},{"name":"Interdipartmental University Center of Research \u201cAdaptation and Regeneration of Tissues and Organs (ARTO)\u201d, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7768-0794","authenticated-orcid":false,"given":"Ilaria","family":"Grossi","sequence":"additional","affiliation":[{"name":"Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Garc\u00eda-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d (CSIC-UAM), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7495-809X","authenticated-orcid":false,"given":"Gaurangkumar","family":"Patel","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d (CSIC-UAM), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6993-1565","authenticated-orcid":false,"given":"Alessandro","family":"Salvi","sequence":"additional","affiliation":[{"name":"Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7646-3592","authenticated-orcid":false,"given":"Antonio","family":"Lavazza","sequence":"additional","affiliation":[{"name":"Instituto Zooprofilattico Sperimentale della Lombardia ed Emilia-Romagna (IZSLER), 25124 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9306-0851","authenticated-orcid":false,"given":"Giuseppina","family":"De Petro","sequence":"additional","affiliation":[{"name":"Division of Biology and Genetics, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2796-1453","authenticated-orcid":false,"given":"Maria","family":"Monsalve","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biom\u00e9dicas \u201cAlberto Sols\u201d (CSIC-UAM), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7515-5846","authenticated-orcid":false,"given":"Rita","family":"Rezzani","sequence":"additional","affiliation":[{"name":"Division of Anatomy and Physiopathology, Department of Clinical and Experimental Sciences, University of Brescia, Viale Europa 11, 25123 Brescia, Italy"},{"name":"Interdipartmental University Center of Research \u201cAdaptation and Regeneration of Tissues and Organs (ARTO)\u201d, University of Brescia, 25123 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1007\/978-3-319-48382-5_19","article-title":"Non-Alcoholic Fatty Liver Disease","volume":"960","author":"Engin","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1146\/annurev-pathol-121808-102132","article-title":"Nonalcoholic Fatty Liver Disease: Pathology and Pathogenesis","volume":"5","author":"Tiniakos","year":"2010","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.cgh.2015.07.019","article-title":"Hepatocellular Carcinoma in the Absence of Cirrhosis in United States Veterans Is Associated with Nonalcoholic Fatty Liver Disease","volume":"14","author":"Mittal","year":"2016","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.jhep.2018.10.033","article-title":"Non-alcoholic fatty liver disease\u2014A global public health perspective","volume":"70","author":"Younossi","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1146\/annurev-pathol-020117-043617","article-title":"Recent Insights into the Pathogenesis of Nonalcoholic Fatty Liver Disease","volume":"13","author":"Arab","year":"2018","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3389\/fphys.2018.00193","article-title":"The Biological Clock: A Pivotal Hub in Non-alcoholic Fatty Liver Disease Pathogenesis","volume":"9","author":"Mazzoccoli","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1194\/jlr.R066514","article-title":"Lipid signaling and lipotoxicity in metaflammation: Indications for metabolic disease pathogenesis and treatment","volume":"57","author":"Ertunc","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.jhep.2018.06.008","article-title":"Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease","volume":"69","author":"Lebeaupin","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1053\/j.gastro.2015.09.042","article-title":"Regulation of Liver Metabolism by Autophagy","volume":"150","author":"Cuervo","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.biochi.2013.06.007","article-title":"Zonation of glucose and fatty acid metabolism in the liver: Mechanism and metabolic consequences","volume":"96","author":"Hijmans","year":"2014","journal-title":"Biochimie"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1179","DOI":"10.1038\/cddis.2014.162","article-title":"Impaired autophagic flux is associated with increased endoplasmic reticulum stress during the development of NAFLD","volume":"5","author":"Mayoral","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/s41574-018-0009-1","article-title":"Targeting autophagy in obesity: From pathophysiology to management","volume":"14","author":"Zhang","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"637027","DOI":"10.1155\/2014\/637027","article-title":"Nonalcoholic Fatty liver disease: Pathogenesis and therapeutics from a mitochondria-centric perspective","volume":"2014","author":"Gusdon","year":"2014","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.lfs.2017.11.019","article-title":"Mitochondrial dysfunction in obesity","volume":"192","author":"Costa","year":"2018","journal-title":"Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.biocel.2017.12.019","article-title":"Mitochondria in non-alcoholic fatty liver disease","volume":"95","author":"Fontes","year":"2018","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"243","DOI":"10.5487\/TR.2014.30.4.243","article-title":"Mitophagy: Therapeutic potentials for liver disease and beyond","volume":"30","author":"Lee","year":"2014","journal-title":"Toxicol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"87","DOI":"10.14348\/molcells.2016.2318","article-title":"Sirt1 and the Mitochondria","volume":"39","author":"Tang","year":"2016","journal-title":"Mol. Cells"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"12861","DOI":"10.1073\/pnas.0702509104","article-title":"Fasting-dependent glucose and lipid metabolic response through hepatic sirtuin 1","volume":"104","author":"Rodgers","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.celrep.2017.03.026","article-title":"ATGL Promotes Autophagy\/Lipophagy via SIRT1 to Control Hepatic Lipid Droplet Catabolism","volume":"19","author":"Sathyanarayan","year":"2017","journal-title":"Cell Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1096\/fj.10-173492","article-title":"Hepatic overexpression of SIRT1 in mice attenuates endoplasmic reticulum stress and insulin resistance in the liver","volume":"25","author":"Li","year":"2011","journal-title":"FASEB J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"33959","DOI":"10.1074\/jbc.M110.122978","article-title":"SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism","volume":"285","author":"Ponugoti","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Liou, C.-J., Lee, Y.-K., Ting, N.-C., Chen, Y.-L., Shen, S.-C., Wu, S.-J., and Huang, W.-C. (2019). Protective Effects of Licochalcone A Ameliorates Obesity and Non-Alcoholic Fatty Liver Disease Via Promotion of the Sirt-1\/AMPK Pathway in Mice Fed a High-Fat Diet. Cells, 8.","DOI":"10.3390\/cells8050447"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2504","DOI":"10.1210\/en.2009-1013","article-title":"Lack of SIRT1 (Mammalian Sirtuin 1) Activity Leads to Liver Steatosis in the SIRT1 +\/\u2212 Mice: A Role of Lipid Mobilization and Inflammation","volume":"151","author":"Xu","year":"2010","journal-title":"Endocrinology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1007\/s12020-014-0465-x","article-title":"Plasma levels of SIRT1 associate with non-alcoholic fatty liver disease in obese patients","volume":"49","author":"Mariani","year":"2015","journal-title":"Endocrine"},{"key":"ref_25","first-page":"410","article-title":"Direct evidence of sirtuin downregulation in the liver of non-alcoholic fatty liver disease patients","volume":"44","author":"Wu","year":"2014","journal-title":"Ann. Clin. Lab. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3389\/fphys.2012.00068","article-title":"MicroRNA Regulation of SIRT1","volume":"3","author":"Yamakuchi","year":"2012","journal-title":"Front. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"527","DOI":"10.18632\/aging.100184","article-title":"Controlling SIRT1 expression by microRNAs in health and metabolic disease","volume":"2","author":"Lee","year":"2010","journal-title":"Aging"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"13421","DOI":"10.1073\/pnas.0801613105","article-title":"miR-34a repression of SIRT1 regulates apoptosis","volume":"105","author":"Yamakuchi","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"12604","DOI":"10.1074\/jbc.M109.094524","article-title":"A pathway involving farnesoid X receptor and small heterodimer partner positively regulates hepatic sirtuin 1 levels via microRNA-34a inhibition","volume":"285","author":"Lee","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"13729","DOI":"10.1038\/srep13729","article-title":"Effect of MIR-34a in regulating steatosis by targeting PPAR\u03b1 expression in nonalcoholic fatty liver disease","volume":"5","author":"Ding","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1038\/labinvest.2010.113","article-title":"Difference in expression of hepatic microRNAs miR-29c, miR-34a, miR-155, and miR-200b is associated with strain-specific susceptibility to dietary nonalcoholic steatohepatitis in mice","volume":"90","author":"Pogribny","year":"2010","journal-title":"Lab. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jhep.2012.08.008","article-title":"miR-34a\/SIRT1\/p53 is suppressed by ursodeoxycholic acid in the rat liver and activated by disease severity in human non-alcoholic fatty liver disease","volume":"58","author":"Castro","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.1600-079X.2011.00931.x","article-title":"Extrapineal melatonin: Analysis of its subcellular distribution and daily fluctuations","volume":"52","author":"Venegas","year":"2012","journal-title":"J. Pineal Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.phrs.2009.11.014","article-title":"Evidence of melatonin synthesis and release by mast cells. Possible modulatory role on inflammation","volume":"62","author":"Maldonado","year":"2010","journal-title":"Pharmacol. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1007\/s00018-017-2609-7","article-title":"Melatonin as a mitochondria-targeted antioxidant: One of evolution\u2019s best ideas","volume":"74","author":"Reiter","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_36","first-page":"7515767","article-title":"Potential Crosstalk between Fructose and Melatonin: A New Role of Melatonin-Inhibiting the Metabolic Effects of Fructose","volume":"2018","year":"2018","journal-title":"Int. J. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Tan, D.-X., Manchester, L.C., Qin, L., and Reiter, R.J. (2016). Melatonin: A Mitochondrial Targeting Molecule Involving Mitochondrial Protection and Dynamics. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17122124"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1097\/WNR.0000000000001139","article-title":"Mitochondrial biogenesis mediated by melatonin in an APPswe\/PS1dE9 transgenic mice model","volume":"29","author":"Song","year":"2018","journal-title":"Neuroreport"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1111\/jpi.12019","article-title":"Analysis of the daily changes of melatonin receptors in the rat liver","volume":"54","author":"Venegas","year":"2013","journal-title":"J. Pineal Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Stacchiotti, A., Favero, G., Lavazza, A., Golic, I., Aleksic, M., Korac, A., Rodella, L.F., and Rezzani, R. (2016). Hepatic Macrosteatosis Is Partially Converted to Microsteatosis by Melatonin Supplementation in ob\/ob Mice Non-Alcoholic Fatty Liver Disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148115"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7968452","DOI":"10.1155\/2018\/7968452","article-title":"Melatonin Modulation of Sirtuin-1 Attenuates Liver Injury in a Hypercholesterolemic Mouse Model","volume":"2018","author":"Bonomini","year":"2018","journal-title":"BioMed Res. Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e12391","DOI":"10.1111\/jpi.12391","article-title":"Melatonin and sirtuins: A \u201cnot-so unexpected\u201d relationship","volume":"62","author":"Mayo","year":"2017","journal-title":"J. Pineal Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Machado, M.V., Michelotti, G.A., Xie, G., de Almeida, T.P., Boursier, J., Bohnic, B., Guy, C.D., Diehl, A.M., and Diehl, A.M. (2015). Mouse Models of Diet-Induced Nonalcoholic Steatohepatitis Reproduce the Heterogeneity of the Human Disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132315"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Van Herck, M., Vonghia, L., and Francque, S. (2017). Animal Models of Nonalcoholic Fatty Liver Disease\u2014A Starter\u2019s Guide. Nutrients, 9.","DOI":"10.3390\/nu9101072"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Henkel, J., Alfine, E., Sa\u00edn, J., J\u00f6hrens, K., Weber, D., Castro, J., K\u00f6nig, J., Stuhlmann, C., Vahrenbrink, M., and Jonas, W. (2018). Soybean Oil-Derived Poly-Unsaturated Fatty Acids Enhance Liver Damage in NAFLD Induced by Dietary Cholesterol. Nutrients, 10.","DOI":"10.3390\/nu10091326"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.jhep.2016.05.005","article-title":"A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer","volume":"65","author":"Asgharpour","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.jhep.2018.05.002","article-title":"Towards a definite mouse model of NAFLD","volume":"69","author":"Castro","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/j.lfs.2012.11.011","article-title":"Endothelial and vascular smooth muscle cell dysfunction mediated by cyclophylin A and the atheroprotective effects of melatonin","volume":"92","author":"Rezzani","year":"2013","journal-title":"Life Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"727","DOI":"10.4161\/auto.7.7.15371","article-title":"Liver autophagy contributes to the maintenance of blood glucose and amino acid levels","volume":"7","author":"Ezaki","year":"2011","journal-title":"Autophagy"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.2337\/db16-0924","article-title":"Butyrate Regulates Liver Mitochondrial Function, Efficiency, and Dynamics in Insulin-Resistant Obese Mice","volume":"66","author":"Mollica","year":"2017","journal-title":"Diabetes"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4161\/auto.1.1.1270","article-title":"Maturation of autophagic vacuoles in Mammalian cells","volume":"1","author":"Eskelinen","year":"2005","journal-title":"Autophagy"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.3892\/ijo.2015.2923","article-title":"Molecular characterization of LASP-1 expression reveals vimentin as its new partner in human hepatocellular carcinoma cells","volume":"46","author":"Salvi","year":"2015","journal-title":"Int. J. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6955","DOI":"10.18632\/oncotarget.14332","article-title":"Clinical and biological significance of miR-23b and miR-193a in human hepatocellular carcinoma","volume":"8","author":"Grossi","year":"2017","journal-title":"Oncotarget"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative C(T) method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1177\/1535370213489446","article-title":"Role of p62\/SQSTM1 in liver physiology and pathogenesis","volume":"238","author":"Manley","year":"2013","journal-title":"Exp. Biol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"16774","DOI":"10.1038\/srep16774","article-title":"Isocaloric Pair-Fed High-Carbohydrate Diet Induced More Hepatic Steatosis and Inflammation than High-Fat Diet Mediated by miR-34a\/SIRT1 Axis in Mice","volume":"5","author":"Li","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1093\/toxsci\/kfu164","article-title":"Melatonin Improves Mitochondrial Function by Promoting MT1\/SIRT1\/PGC-1 Alpha-Dependent Mitochondrial Biogenesis in Cadmium-Induced Hepatotoxicity In Vitro","volume":"142","author":"Guo","year":"2014","journal-title":"Toxicol. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e12491","DOI":"10.1111\/jpi.12491","article-title":"Melatonin prevents Drp1-mediated mitochondrial fission in diabetic hearts through SIRT1-PGC1\u03b1 pathway","volume":"65","author":"Ding","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1111\/jpi.12354","article-title":"Melatonin modulates neonatal brain inflammation through endoplasmic reticulum stress, autophagy, and miR-34a\/silent information regulator 1 pathway","volume":"61","author":"Carloni","year":"2016","journal-title":"J. Pineal Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"40","DOI":"10.4103\/2277-9175.204593","article-title":"The Effects of Melatonin in Patients with Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial","volume":"6","author":"Pakravan","year":"2017","journal-title":"Adv. Biomed. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1111\/j.1600-079X.2006.00346.x","article-title":"Melatonin ameliorates nonalcoholic fatty liver induced by high-fat diet in rats","volume":"41","author":"Pan","year":"2006","journal-title":"J. Pineal Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Bonomini, F., Borsani, E., Favero, G., Rodella, L.F., and Rezzani, R. (2018). Dietary Melatonin Supplementation Could Be a Promising Preventing\/Therapeutic Approach for a Variety of Liver Diseases. Nutrients, 10.","DOI":"10.3390\/nu10091135"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.tem.2018.03.008","article-title":"Functional Interaction between Melatonin Signaling and Noncoding RNAs","volume":"29","author":"Su","year":"2018","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Tessitore, A., Cicciarelli, G., Del Vecchio, F., Gaggiano, A., Verzella, D., Fischietti, M., Mastroiaco, V., Vetuschi, A., Sferra, R., and Barnabei, R. (2016). MicroRNA expression analysis in high fat diet-induced NAFLD-NASH-HCC progression: Study on C57BL\/6J mice. BMC Cancer, 16.","DOI":"10.1186\/s12885-015-2007-1"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"16137","DOI":"10.1073\/pnas.1205951109","article-title":"Aberrantly elevated microRNA-34a in obesity attenuates hepatic responses to FGF19 by targeting a membrane coreceptor \u03b2-Klotho","volume":"109","author":"Fu","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Ding, S., Jiang, J., Zhang, G., Bu, Y., Zhang, G., and Zhao, X. (2017). Resveratrol and caloric restriction prevent hepatic steatosis by regulating SIRT1-autophagy pathway and alleviating endoplasmic reticulum stress in high-fat diet-fed rats. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0183541"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1038\/s41467-017-01878-6","article-title":"Hepatic Crtc2 controls whole body energy metabolism via a miR-34a-Fgf21 axis","volume":"8","author":"Han","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Knebel, B., Haas, J., Hartwig, S., Jacob, S., K\u00f6llmer, C., Nitzgen, U., Muller\u2013Wieland, D., and Kotzka, J. (2012). Liver-Specific Expression of Transcriptionally Active SREBP-1c Is Associated with Fatty Liver and Increased Visceral Fat Mass. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031812"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"33028","DOI":"10.1074\/jbc.M109.089391","article-title":"Time of day and nutrients in feeding govern daily expression rhythms of the gene for sterol regulatory element-binding protein (SREBP)-1 in the mouse liver","volume":"285","author":"Matsumoto","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.molmet.2016.11.002","article-title":"Celastrol ameliorates liver metabolic damage caused by a high-fat diet through Sirt1","volume":"6","author":"Zhang","year":"2017","journal-title":"Mol. Metab."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1002\/oby.21393","article-title":"Diet-induced obesity and insulin resistance are associated with brown fat degeneration in SIRT1-deficient mice","volume":"24","author":"Xu","year":"2016","journal-title":"Obesity"},{"key":"ref_73","first-page":"G632","article-title":"Decreasing mitochondrial fission alleviates hepatic steatosis in a murine model of nonalcoholic fatty liver disease","volume":"307","author":"Galloway","year":"2014","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.lfs.2018.04.022","article-title":"Oleic acid protects saturated fatty acid mediated lipotoxicity in hepatocytes and rat of non-alcoholic steatohepatitis","volume":"203","author":"Chen","year":"2018","journal-title":"Life Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"eaao4617","DOI":"10.1126\/scisignal.aao4617","article-title":"IRE1\u03b1 prevents hepatic steatosis by processing and promoting the degradation of select microRNAs","volume":"11","author":"Wang","year":"2018","journal-title":"Sci. Signal"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/j.jhep.2016.07.002","article-title":"The inflammasome in liver disease","volume":"65","author":"Wree","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/j.jhep.2018.02.013","article-title":"The role of Kupffer cells in hepatic iron and lipid metabolism","volume":"69","author":"Scott","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e12534","DOI":"10.1111\/jpi.12534","article-title":"Therapeutic potential of melatonin related to its role as an autophagy regulator: A review","volume":"66","author":"Boga","year":"2019","journal-title":"J. Pineal Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4108","DOI":"10.1038\/s41598-018-22339-0","article-title":"Celecoxib alleviates nonalcoholic fatty liver disease by restoring autophagic flux","volume":"8","author":"Liu","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.ejphar.2015.11.012","article-title":"Protective role of autophagy in methionine-choline deficient diet-induced advanced nonalcoholic steatohepatitis in mice","volume":"770","author":"Chen","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e12450","DOI":"10.1111\/jpi.12450","article-title":"Effects of melatonin on fatty liver disease: The role of NR4A1\/DNA-PKcs\/p53 pathway, mitochondrial fission, and mitophagy","volume":"64","author":"Zhou","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1096\/fj.201601393R","article-title":"Defective lysosomal clearance of autophagosomes and its clinical implications in nonalcoholic steatohepatitis","volume":"32","author":"Wang","year":"2018","journal-title":"FASEB J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/cdd.2015.96","article-title":"Sirtuin 1 suppresses mitochondrial dysfunction of ischemic mouse livers in a mitofusin 2-dependent manner","volume":"23","author":"Biel","year":"2016","journal-title":"Cell Death Differ."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.cmet.2018.06.014","article-title":"Mitochondrial Stasis Reveals p62-Mediated Ubiquitination in Parkin-Independent Mitophagy and Mitigates Nonalcoholic Fatty Liver Disease","volume":"28","author":"Yamada","year":"2018","journal-title":"Cell Metab."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"10084","DOI":"10.3748\/wjg.v22.i46.10084","article-title":"Sirtuins and nonalcoholic fatty liver disease","volume":"22","author":"Nassir","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1111\/jpi.12104","article-title":"Melatonin administration decreases adipogenesis in the liver of ob\/ob mice through autophagy modulation","volume":"56","author":"Caballero","year":"2014","journal-title":"J. Pineal Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.bbrc.2017.09.042","article-title":"MiR-181b regulates steatosis in nonalcoholic fatty liver disease via targeting SIRT1","volume":"493","author":"Wang","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e12509","DOI":"10.1111\/jpi.12509","article-title":"A congenic line of the C57BL\/6J mouse strain that is proficient in melatonin synthesis","volume":"65","author":"Zhang","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"101150","DOI":"10.1016\/j.redox.2019.101150","article-title":"Improved mass spectrometry-based activity assay reveals oxidative and metabolic stress as sirtuin-1 regulators","volume":"22","author":"Shao","year":"2019","journal-title":"Redox Biol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/9\/1053\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:17:42Z","timestamp":1760188662000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/9\/1053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,8]]},"references-count":89,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["cells8091053"],"URL":"https:\/\/doi.org\/10.3390\/cells8091053","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,8]]}}}