{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:19:01Z","timestamp":1784557141459,"version":"3.55.0"},"reference-count":38,"publisher":"Bioscientifica","issue":"3","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,10,1]]},"abstract":"<jats:p>\n                    Medium-chain acyl-CoA dehydrogenase (MCAD) is one of the significant enzymes involved in the \u03b2-oxidation of mitochondrial fatty acids. MCAD deficiency affects the \u03b2-oxidation of fatty acid and leads to lipid deposition in multiple organs, but little is known about its importance in nonalcoholic steatohepatitis (NASH). Empagliflozin is revealed to effectively improve NASH by increasing research, whereas the specific mechanism still has to be explored. Human liver tissues of patients with or without NASH were obtained for proteomic analysis to screen proteins of interest. db\/db mice were given empagliflozin by gavage for 8 weeks. The expression of MCAD and signaling molecules involved in hepatic lipid metabolism was evaluated in human liver, mice and HL7702 cells. We found that the MCAD levels in the liver were significantly reduced in NASH patients compared to patients without NASH. Protein\u2013protein interaction network analysis showed that MCAD was highly correlated with forkhead box A2 (FOXA2) and protein kinase AMP-activated catalytic subunit alpha (PRKAA). AMPK\/FOXA2\/MCAD signaling pathway was detected to be inhibited in the liver of NASH patients. Decreased expression of MCAD was also observed in the livers of db\/db mice and hepatocyte treated with palmitic acid and glucose. Of note, empagliflozin could upregulate MCAD expression by activating AMPK\/FOXA2 signaling pathway, reduce lipid deposition and improve NASH\n                    <jats:italic>in vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    . This research demonstrated that MCAD is a key player of hepatic lipid deposition and its targeting partially corrects NASH. MCAD thus may be a potential therapeutic target for the treatment of NASH.\n                  <\/jats:p>","DOI":"10.1530\/jme-22-0022","type":"journal-article","created":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T11:19:04Z","timestamp":1659007144000},"page":"415-430","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":7,"title":["MCAD activation by empagliflozin promotes fatty acid oxidation and reduces lipid deposition in NASH"],"prefix":"10.1530","volume":"69","author":[{"given":"Yi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi-Ling","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, China"},{"name":"NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Pathology, The Third Central Clinical College of Tianjin Medical University, Tianjin Third Central Hospital, Tianjin Key Laboratory of Artificial Cells, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Sun","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian-Hua","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Xin","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Yan","family":"Niu","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Na","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4857-8146","authenticated-orcid":true,"given":"Chun-Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib2","series-title":"Cardiovascular Diabetology","article-title":"Sodium-glucose cotransporter 2 inhibitor Dapagliflozin attenuates diabetic cardiomyopathy","volume":"19","author":"Arow","year":"2020","unstructured":"Arow MWaldman MYadin DNudelman VShainberg AAbraham NGFreimark DKornowski RAravot DHochhauser E2020Sodium-glucose cotransporter 2 inhibitor Dapagliflozin attenuates diabetic cardiomyopathy. Cardiovascular Diabetology19 7. (https:\/\/doi.org\/10.1186\/s12933-019-0980-4)31924211"},{"key":"bib3","series-title":"Clinical Pharmacology and Therapeutics","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1038\/clpt.2010.2","article-title":"Nuclear receptors, inflammation, and liver disease: insights for cholestatic and fatty liver diseases","volume":"87","author":"Arrese","year":"2010","unstructured":"Arrese MKarpen SJ2010Nuclear receptors, inflammation, and liver disease: insights for cholestatic and fatty liver diseases. Clinical Pharmacology and Therapeutics87473\u2013478. (https:\/\/doi.org\/10.1038\/clpt.2010.2)2020051510.1038\/clpt.2010.2"},{"key":"bib4","series-title":"Journal of Virology","doi-asserted-by":"publisher","first-page":"4195","DOI":"10.1128\/JVI.03327-13","article-title":"Forkhead box transcription factor regulation and lipid accumulation by hepatitis C virus","volume":"88","author":"Bose","year":"2014","unstructured":"Bose SKKim HMeyer KWolins NDavidson NORay R2014Forkhead box transcription factor regulation and lipid accumulation by hepatitis C virus. Journal of Virology884195\u20134203. (https:\/\/doi.org\/10.1128\/JVI.03327-13)2447843810.1128\/JVI.03327-13"},{"key":"bib5","series-title":"Transgenic Research","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1007\/s11248-011-9579-6","article-title":"Altered glucose-stimulated insulin secretion in a mouse line with activated polyamine catabolism","volume":"21","author":"Cerrada-Gimenez","year":"2012","unstructured":"Cerrada-Gimenez MTusa MCasellas APirinen EMoya MBosch FAlhonen L2012Altered glucose-stimulated insulin secretion in a mouse line with activated polyamine catabolism. Transgenic Research21843\u2013853. (https:\/\/doi.org\/10.1007\/s11248-011-9579-6)10.1007\/s11248-011-9579-6"},{"key":"bib6","series-title":"Biomedicine and Pharmacotherapy","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.biopha.2018.11.069","article-title":"Wuzhi capsule (Schisandra Sphenanthera extract) attenuates liver steatosis and inflammation during non-alcoholic fatty liver disease development","volume":"110","author":"Chen","year":"2019","unstructured":"Chen ZLiu FZheng NGuo MBao LZhan YZhang MZhao YGuo WDing G2019Wuzhi capsule (Schisandra Sphenanthera extract) attenuates liver steatosis and inflammation during non-alcoholic fatty liver disease development. Biomedicine and Pharmacotherapy110285\u2013293. (https:\/\/doi.org\/10.1016\/j.biopha.2018.11.069)3052201410.1016\/j.biopha.2018.11.069"},{"key":"bib7","series-title":"Lancet: Diabetes and Endocrinology","first-page":"610","article-title":"Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease: an exploratory analysis from the EMPA-REG OUTCOME randomised, placebo-controlled trial","volume":"5","author":"Cherney","year":"2017","unstructured":"Cherney DZIZinman BInzucchi SEKoitka-Weber AMattheus MVon Eynatten MWanner C2017Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease: an exploratory analysis from the EMPA-REG OUTCOME randomised, placebo-controlled trial. Lancet: Diabetes and Endocrinology5610\u2013621. (https:\/\/doi.org\/10.1016\/S2213-8587(1730182-1)28666775"},{"key":"bib8","series-title":"Molecular Biology of the Cell","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1091\/mbc.E18-03-0155","article-title":"Phosphorylation of MCAD selectively rescues PINK1 deficiencies in behavior and metabolism","volume":"29","author":"Course","year":"2018","unstructured":"Course MMScott AISchoor CHsieh CHPapakyrikos AMWinter DCowan TMWang X2018Phosphorylation of MCAD selectively rescues PINK1 deficiencies in behavior and metabolism. Molecular Biology of the Cell291219\u20131227. (https:\/\/doi.org\/10.1091\/mbc.E18-03-0155)2956325410.1091\/mbc.E18-03-0155"},{"key":"bib9","series-title":"Archives of Biochemistry and Biophysics","article-title":"Oxidative damage in mitochondrial fatty acids oxidation disorders patients and the in vitro effect of l-carnitine on DNA damage induced by the accumulated metabolites","volume":"679","author":"de Moraes","year":"2020","unstructured":"de Moraes MSGuerreiro GSitta ADe Moura Coelho DManfredini VWajner MVargas CR2020Oxidative damage in mitochondrial fatty acids oxidation disorders patients and the in vitro effect of l-carnitine on DNA damage induced by the accumulated metabolites. Archives of Biochemistry and Biophysics679 108206. (https:\/\/doi.org\/10.1016\/j.abb.2019.108206)31760122"},{"key":"bib10","series-title":"Anaesthesia","article-title":"MCAD deficiency and anaesthesia","volume":"50","author":"Dearlove","year":"1995","unstructured":"Dearlove ORPerkins R1995MCAD deficiency and anaesthesia. Anaesthesia50 265. (https:\/\/doi.org\/10.1111\/j.1365-2044.1995.tb04584.x)7717506"},{"key":"bib11","series-title":"Journal of Hepatology","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1016\/j.jhep.2017.06.003","article-title":"New trends on obesity and NAFLD in Asia","volume":"67","author":"Fan","year":"2017","unstructured":"Fan JGKim SUWong VW2017New trends on obesity and NAFLD in Asia. Journal of Hepatology67862\u2013873. (https:\/\/doi.org\/10.1016\/j.jhep.2017.06.003)2864205910.1016\/j.jhep.2017.06.003"},{"key":"bib12","series-title":"Diabetology and Metabolic Syndrome","article-title":"Empagliflozin (an SGLT2 inhibitor), alone or in combination with linagliptin (a DPP-4 inhibitor), prevents steatohepatitis in a novel mouse model of non-alcoholic steatohepatitis and diabetes","volume":"8","author":"Jojima","year":"2016","unstructured":"Jojima TTomotsune TIijima TAkimoto KSuzuki KAso Y2016Empagliflozin (an SGLT2 inhibitor), alone or in combination with linagliptin (a DPP-4 inhibitor), prevents steatohepatitis in a novel mouse model of non-alcoholic steatohepatitis and diabetes. Diabetology and Metabolic Syndrome8 45. (https:\/\/doi.org\/10.1186\/s13098-016-0169-x)"},{"key":"bib13","series-title":"European Journal of Pharmacology","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.ejphar.2018.03.043","article-title":"Canagliflozin protects against non-alcoholic steatohepatitis in type-2 diabetic rats through zinc alpha-2 glycoprotein up-regulation","volume":"828","author":"Kabil","year":"2018","unstructured":"Kabil SLMahmoud NM2018Canagliflozin protects against non-alcoholic steatohepatitis in type-2 diabetic rats through zinc alpha-2 glycoprotein up-regulation. European Journal of Pharmacology828135\u2013145. (https:\/\/doi.org\/10.1016\/j.ejphar.2018.03.043)2960889810.1016\/j.ejphar.2018.03.043"},{"key":"bib14","series-title":"PLoS ONE","article-title":"Ipragliflozin improves hepatic steatosis in obese mice and liver dysfunction in type 2 diabetic patients irrespective of body weight reduction","volume":"11","author":"Komiya","year":"2016","unstructured":"Komiya CTsuchiya KShiba KMiyachi YFuruke SShimazu NYamaguchi SKanno KOgawa Y2016Ipragliflozin improves hepatic steatosis in obese mice and liver dysfunction in type 2 diabetic patients irrespective of body weight reduction. PLoS ONE11 e0151511. (https:\/\/doi.org\/10.1371\/journal.pone.0151511)26977813"},{"key":"bib15","series-title":"Diabetes Care","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.2337\/dc18-0165","article-title":"Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: a randomized controlled trial (E-LIFT Trial)","volume":"41","author":"Kuchay","year":"2018","unstructured":"Kuchay MSKrishan SMishra SKFarooqui KJSingh MKWasir JSBansal BKaur PJevalikar GGill HK2018Effect of empagliflozin on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease: a randomized controlled trial (E-LIFT Trial). Diabetes Care411801\u20131808. (https:\/\/doi.org\/10.2337\/dc18-0165)2989555710.2337\/dc18-0165"},{"key":"bib16","series-title":"Annals of Translational Medicine","article-title":"The SGLT2 inhibitor dapagliflozin attenuates the activity of ROS-NLRP3 inflammasome axis in steatohepatitis with diabetes mellitus","volume":"7","author":"Leng","year":"2019","unstructured":"Leng WWu MPan HLei XChen LWu QOuyang XLiang Z2019The SGLT2 inhibitor dapagliflozin attenuates the activity of ROS-NLRP3 inflammasome axis in steatohepatitis with diabetes mellitus. Annals of Translational Medicine7 429. (https:\/\/doi.org\/10.21037\/atm.2019.09.03)31700865"},{"key":"bib17","series-title":"Gastroenterology","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1053\/j.gastro.2013.10.059","article-title":"Hepatic SIRT1 attenuates hepatic steatosis and controls energy balance in mice by inducing fibroblast growth factor 21","volume":"146","author":"Li","year":"2014","unstructured":"Li YWong KGiles AJiang JLee JWAdams ACKharitonenkov AYang QGao BGuarente L2014Hepatic SIRT1 attenuates hepatic steatosis and controls energy balance in mice by inducing fibroblast growth factor 21. Gastroenterology146539.e7\u2013549.e7. (https:\/\/doi.org\/10.1053\/j.gastro.2013.10.059)2418481110.1053\/j.gastro.2013.10.059"},{"key":"bib18","series-title":"Lancet: Gastroenterology and Hepatology","first-page":"389","article-title":"Prevalence, incidence, and outcome of non-alcoholic fatty liver disease in Asia, 1999\u20132019: a systematic review and meta-analysis","volume":"4","author":"Li","year":"2019a","unstructured":"Li JZou BYeo YHFeng YXie XLee DHFujii HWu YKam LYJi F2019aPrevalence, incidence, and outcome of non-alcoholic fatty liver disease in Asia, 1999\u20132019: a systematic review and meta-analysis. Lancet: Gastroenterology and Hepatology4389\u2013398. (https:\/\/doi.org\/10.1016\/S2468-1253(1930039-1)"},{"key":"bib19","series-title":"Theranostics","doi-asserted-by":"publisher","first-page":"7599","DOI":"10.7150\/thno.34931","article-title":"Yin Yang 1 facilitates hepatocellular carcinoma cell lipid metabolism and tumor progression by inhibiting PGC-1\u03b2-induced fatty acid oxidation","volume":"9","author":"Li","year":"2019b","unstructured":"Li YKasim VYan XLi LMeliala ITSHuang CLi ZLei KSong GZheng X2019bYin Yang 1 facilitates hepatocellular carcinoma cell lipid metabolism and tumor progression by inhibiting PGC-1\u03b2-induced fatty acid oxidation. Theranostics97599\u20137615. (https:\/\/doi.org\/10.7150\/thno.34931)10.7150\/thno.34931"},{"key":"bib20","series-title":"Clinics in Liver Disease","doi-asserted-by":"publisher","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","unstructured":"Marengo AJouness RIBugianesi E2016Progression and natural history of nonalcoholic fatty liver disease in adults. Clinics in Liver Disease20313\u2013324. (https:\/\/doi.org\/10.1016\/j.cld.2015.10.010)2706327110.1016\/j.cld.2015.10.010"},{"key":"bib21","series-title":"GeneReviews","article-title":"Medium-chain acyl-coenzyme A dehydrogenase deficiency","author":"Merritt","year":"1993","unstructured":"Merritt JL 2nd& Chang IJ1993Medium-chain acyl-coenzyme A dehydrogenase deficiency. In GeneReviews. Eds Adam MPArdinger HHPagon RAWallace SEBean LJHMirzaa GAmemiya A. Seattle, WA, USA: University of Washington."},{"key":"bib22","series-title":"Annual Review of Medicine","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1146\/annurev.med.60.101107.134820","article-title":"Emerging molecular targets for the treatment of nonalcoholic fatty liver disease","volume":"61","author":"Musso","year":"2010","unstructured":"Musso GGambino RCassader M2010Emerging molecular targets for the treatment of nonalcoholic fatty liver disease. Annual Review of Medicine61375\u2013392. (https:\/\/doi.org\/10.1146\/annurev.med.60.101107.134820)2005934410.1146\/annurev.med.60.101107.134820"},{"key":"bib23","series-title":"JCI Insight","article-title":"SGLT2 inhibition reprograms systemic metabolism via FGF21-dependent and -independent mechanisms","volume":"4","author":"Osataphan","year":"2019","unstructured":"Osataphan SMacchi CSinghal GChimene-Weiss JSales VKozuka CDreyfuss JMPan HTangcharoenpaisan YMorningstar J2019SGLT2 inhibition reprograms systemic metabolism via FGF21-dependent and -independent mechanisms. JCI Insight4 SGLT2. (https:\/\/doi.org\/10.1172\/jci.insight.123130)30843877"},{"key":"bib24","series-title":"Journal of Ethnopharmacology","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.jep.2018.12.034","article-title":"Chronic treatment with the modified Longdan Xiegan Tang attenuates olanzapine-induced fatty liver in rats by regulating hepatic de novo lipogenesis and fatty acid beta-oxidation-associated gene expression mediated by SREBP-1c, PPAR-alpha and AMPK-alpha","volume":"232","author":"Ren","year":"2019","unstructured":"Ren LSun DZhou XYang YHuang XLi YWang CLi Y2019Chronic treatment with the modified Longdan Xiegan Tang attenuates olanzapine-induced fatty liver in rats by regulating hepatic de novo lipogenesis and fatty acid beta-oxidation-associated gene expression mediated by SREBP-1c, PPAR-alpha and AMPK-alpha. Journal of Ethnopharmacology232176\u2013187. (https:\/\/doi.org\/10.1016\/j.jep.2018.12.034)3059019710.1016\/j.jep.2018.12.034"},{"key":"bib25","series-title":"Journal of Gastroenterology and Hepatology","first-page":"102","article-title":"PPAR agonists treatment is effective in a nonalcoholic fatty liver disease animal model by modulating fatty-acid metabolic enzymes","volume":"23","author":"Seo","year":"2008","unstructured":"Seo YSKim JHJo NYChoi KMBaik SHPark JJKim JSByun KSBak YTLee CH2008PPAR agonists treatment is effective in a nonalcoholic fatty liver disease animal model by modulating fatty-acid metabolic enzymes. Journal of Gastroenterology and Hepatology23102\u2013109. (https:\/\/doi.org\/10.1111\/j.1440-1746.2006.04819.x)"},{"key":"bib26","series-title":"Diabetologia","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1007\/s00125-019-05071-w","article-title":"Luseogliflozin increases beta cell proliferation through humoral factors that activate an insulin receptor- and IGF-1 receptor-independent pathway","volume":"63","author":"Shirakawa","year":"2020","unstructured":"Shirakawa JTajima KOkuyama TKyohara MTogashi YDe Jesus DFBasile GKin TShapiro AMJKulkarni RN2020Luseogliflozin increases beta cell proliferation through humoral factors that activate an insulin receptor- and IGF-1 receptor-independent pathway. Diabetologia63577\u2013587. (https:\/\/doi.org\/10.1007\/s00125-019-05071-w)3189752610.1007\/s00125-019-05071-w"},{"key":"bib27","series-title":"Clinical Science","doi-asserted-by":"publisher","first-page":"2415","DOI":"10.1042\/CS20190863","article-title":"Dapagliflozin not only improves hepatic injury and pancreatic endoplasmic reticulum stress, but also induces hepatic gluconeogenic enzymes expression in obese rats","volume":"133","author":"Swe","year":"2019","unstructured":"Swe MTThongnak LJaikumkao KPongchaidecha AChatsudthipong VLungkaphin A2019Dapagliflozin not only improves hepatic injury and pancreatic endoplasmic reticulum stress, but also induces hepatic gluconeogenic enzymes expression in obese rats. Clinical Science1332415\u20132430. (https:\/\/doi.org\/10.1042\/CS20190863)10.1042\/CS20190863"},{"key":"bib28","series-title":"Nature Reviews: Gastroenterology and Hepatology","first-page":"32","article-title":"NAFLD and diabetes mellitus","volume":"14","author":"Tilg","year":"2017","unstructured":"Tilg HMoschen ARRoden M2017NAFLD and diabetes mellitus. Nature Reviews: Gastroenterology and Hepatology1432\u201342. (https:\/\/doi.org\/10.1038\/nrgastro.2016.147)27729660"},{"key":"bib29","series-title":"Current Therapeutic Research, Clinical and Experimental","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.curtheres.2017.07.002","article-title":"Effects of dapagliflozin on body composition and liver tests in patients with nonalcoholic steatohepatitis associated with type 2 diabetes mellitus: a prospective, open-label, uncontrolled study","volume":"87","author":"Tobita","year":"2017","unstructured":"Tobita HSato SMiyake TIshihara SKinoshita Y2017Effects of dapagliflozin on body composition and liver tests in patients with nonalcoholic steatohepatitis associated with type 2 diabetes mellitus: a prospective, open-label, uncontrolled study. Current Therapeutic Research, Clinical and Experimental8713\u201319. (https:\/\/doi.org\/10.1016\/j.curtheres.2017.07.002)2891290210.1016\/j.curtheres.2017.07.002"},{"key":"bib30","series-title":"Clinical Gastroenterology and Hepatology","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.cgh.2012.03.011","article-title":"Features, diagnosis, and treatment of nonalcoholic fatty liver disease","volume":"10","author":"Torres","year":"2012","unstructured":"Torres DMWilliams CDHarrison SA2012Features, diagnosis, and treatment of nonalcoholic fatty liver disease. Clinical Gastroenterology and Hepatology10837\u2013858. (https:\/\/doi.org\/10.1016\/j.cgh.2012.03.011)2244692710.1016\/j.cgh.2012.03.011"},{"key":"bib31","series-title":"Biochimica et Biophysica Acta","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.bbalip.2009.10.007","article-title":"Fatty liver and lipotoxicity","volume":"1801","author":"Trauner","year":"2010","unstructured":"Trauner MArrese MWagner M2010Fatty liver and lipotoxicity. Biochimica et Biophysica Acta1801299\u2013310. (https:\/\/doi.org\/10.1016\/j.bbalip.2009.10.007)1985760310.1016\/j.bbalip.2009.10.007"},{"key":"bib32","series-title":"Diabetologia","doi-asserted-by":"publisher","first-page":"2134","DOI":"10.1007\/s00125-018-4678-z","article-title":"SGLT2 inhibitors: the future for treatment of type 2 diabetes mellitus and other chronic diseases","volume":"61","author":"Wanner","year":"2018","unstructured":"Wanner CMarx N2018SGLT2 inhibitors: the future for treatment of type 2 diabetes mellitus and other chronic diseases. Diabetologia612134\u20132139. (https:\/\/doi.org\/10.1007\/s00125-018-4678-z)3013203510.1007\/s00125-018-4678-z"},{"key":"bib33","series-title":"Cell Metabolism","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.cmet.2006.01.001","article-title":"Coactivation of Foxa2 through Pgc-1beta promotes liver fatty acid oxidation and triglyceride\/VLDL secretion","volume":"3","author":"Wolfrum","year":"2006","unstructured":"Wolfrum CStoffel M2006Coactivation of Foxa2 through Pgc-1beta promotes liver fatty acid oxidation and triglyceride\/VLDL secretion. Cell Metabolism399\u2013110. (https:\/\/doi.org\/10.1016\/j.cmet.2006.01.001)1645931110.1016\/j.cmet.2006.01.001"},{"key":"bib34","series-title":"Hepatology","doi-asserted-by":"publisher","first-page":"2172","DOI":"10.1002\/hep.31075","article-title":"Letter to the editor: consider more factors when studying risk of cirrhosis and hepatocellular cancer in patients with nonalcoholic fatty liver disease","volume":"71","author":"Yang","year":"2020","unstructured":"Yang NBLi GXChu JGWang YJ2020Letter to the editor: consider more factors when studying risk of cirrhosis and hepatocellular cancer in patients with nonalcoholic fatty liver disease. Hepatology712172\u20132173. (https:\/\/doi.org\/10.1002\/hep.31075)10.1002\/hep.31075"},{"key":"bib35","series-title":"Archives of Biochemistry and Biophysics","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.abb.2011.08.002","article-title":"AMP-activated protein kinase modulates the gene expression of aquaporin 9 via forkhead box a2","volume":"515","author":"Yokoyama","year":"2011","unstructured":"Yokoyama YIguchi KUsui SHirano K2011AMP-activated protein kinase modulates the gene expression of aquaporin 9 via forkhead box a2. Archives of Biochemistry and Biophysics51580\u201388. (https:\/\/doi.org\/10.1016\/j.abb.2011.08.002)2186767610.1016\/j.abb.2011.08.002"},{"key":"bib36","series-title":"Journal of Ethnopharmacology","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.jep.2016.11.020","article-title":"The effects of herbal composition Gambigyeongsinhwan (4) on hepatic steatosis and inflammation in Otsuka Long-Evans Tokushima fatty rats and HepG2 cells","volume":"195","author":"Yoon","year":"2017","unstructured":"Yoon SKim JLee HLee HLim JYang HShin SSYoon M2017The effects of herbal composition Gambigyeongsinhwan (4) on hepatic steatosis and inflammation in Otsuka Long-Evans Tokushima fatty rats and HepG2 cells. Journal of Ethnopharmacology195204\u2013213. (https:\/\/doi.org\/10.1016\/j.jep.2016.11.020)2784526510.1016\/j.jep.2016.11.020"},{"key":"bib37","series-title":"Hepatology","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1002\/hep.28226","article-title":"Identification of novel noninvasive markers for diagnosing nonalcoholic steatohepatitis and related fibrosis by data mining","volume":"63","author":"Yoshimura","year":"2016","unstructured":"Yoshimura KOkanoue TEbise HIwasaki TMizuno MShima TIchihara JYamazaki K2016Identification of novel noninvasive markers for diagnosing nonalcoholic steatohepatitis and related fibrosis by data mining. Hepatology63462\u2013473. (https:\/\/doi.org\/10.1002\/hep.28226)2639004610.1002\/hep.28226"},{"key":"bib38","series-title":"Journal of Hepatology","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/j.jhep.2019.06.021","article-title":"The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: a systematic review and meta-analysis","volume":"71","author":"Younossi","year":"2019","unstructured":"Younossi ZMGolabi PDe Avila LPaik JMSrishord MFukui NQiu YBurns LAfendy ANader F2019The global epidemiology of NAFLD and NASH in patients with type 2 diabetes: a systematic review and meta-analysis. Journal of Hepatology71793\u2013801. (https:\/\/doi.org\/10.1016\/j.jhep.2019.06.021)3127990210.1016\/j.jhep.2019.06.021"},{"key":"bib39","series-title":"New England Journal of Medicine","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.1056\/NEJMoa1504720","article-title":"Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes","volume":"373","author":"Zinman","year":"2015","unstructured":"Zinman BWanner CLachin JMFitchett DBluhmki EHantel SMattheus MDevins TJohansen OEWoerle HJ2015Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. New England Journal of Medicine3732117\u20132128. (https:\/\/doi.org\/10.1056\/NEJMoa1504720)2637897810.1056\/NEJMoa1504720"}],"container-title":["Journal of Molecular Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/jme.bioscientifica.com\/view\/journals\/jme\/69\/3\/JME-22-0022.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/jme.bioscientifica.com\/downloadpdf\/journals\/jme\/69\/3\/JME-22-0022.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/jme.bioscientifica.com\/downloadpdf\/journals\/jme\/69\/3\/JME-22-0022.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:54:11Z","timestamp":1784555651000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/jme\/article\/69\/3\/415-430\/14587"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,1]]},"references-count":38,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.1530\/jme-22-0022","relation":{},"ISSN":["0952-5041","1479-6813"],"issn-type":[{"value":"0952-5041","type":"print"},{"value":"1479-6813","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,1]]}}}