{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T09:08:42Z","timestamp":1793610522205,"version":"4.5.0"},"reference-count":93,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Non-alcoholic fatty liver disease (NAFLD), currently referred to as metabolic dysfunction-associated steatotic liver disease (MASLD), occurring in adults of normal weight, represents a unique emerging phenotype apart from obesity-related NAFLD. Notwithstanding a normal body mass index (BMI), this phenotype poses considerable metabolic and hepatic risk, undermining conventional obesity-focused paradigms of fatty liver disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This comprehensive review integrates global epidemiological data, molecular investigations, and clinical research to elucidate the distinct pathogenesis, risk factors, natural history, and treatment of lean NAFLD. Essential bibliographical databases were screened for research on disease prevalence, genetic determinants, metabolic characteristics, and long-term consequences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Lean NAFLD impacts 5-20% of the worldwide NAFLD population, with a greater frequency in Asian cohorts (~45%). It is characterized by visceral obesity, sarcopenia, and significant genetic determinants (variants of PNPLA3, TM6SF2, and MBOAT7) in normal BMI individuals. Gut dysbiosis and modified bile acid metabolism further delineate its pathophysiology. Importantly, lean NAFLD presents similar or elevated risks for all-cause mortality (1.6-fold increase), advanced fibrosis, cirrhosis, hepatocellular carcinoma, and cardiovascular disease compared to obese NAFLD, despite a lower prevalence of metabolic comorbidities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Lean NAFLD is a clinically relevant condition necessitating customized diagnostic and therapeutic approaches. Lifestyle modifications focusing on moderate weight reduction (3-5%), fructose and cholesterol restrictions, and resistance exercise are highlighted. Future investigations should emphasize consistent classifications, non-invasive biomarkers, and medicines tailored to lean NAFLD phenotypes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2025.1693123","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T13:43:54Z","timestamp":1760967834000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["The emerging phenotype of nonalcoholic fatty liver disease in lean individuals: what\u2019s different?"],"prefix":"10.3389","volume":"16","author":[{"given":"Priyankar","family":"Dey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"147","DOI":"10.15386\/cjmed-993","article-title":"Non-alcoholic fatty liver disease: an update on diagnosis","volume":"91","author":"Dumitrascu","year":"2018","journal-title":"Clujul Med"},{"key":"B2","article-title":"Nonalcoholic steatohepatitis (NASH)","volume-title":"StatPearls","author":"Sharma","year":"2023"},{"key":"B3","doi-asserted-by":"publisher","first-page":"687","DOI":"10.3390\/nu15030687","article-title":"Understanding NAFLD: from case identification to interventions, outcomes, and future perspectives","volume":"15","author":"Clayton-Chubb","year":"2023","journal-title":"Nutrients"},{"key":"B4","doi-asserted-by":"publisher","first-page":"101231","DOI":"10.1016\/j.mam.2023.101231","article-title":"Liver fibrosis in NAFLD\/NASH: from pathophysiology towards diagnostic and therapeutic strategies","volume":"95","author":"Parola","year":"2024","journal-title":"Mol aspects Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2023.0086","article-title":"Changing the nomenclature from nonalcoholic fatty liver disease to metabolic dysfunction-associated fatty liver disease is more than a change in terminology","volume":"29","author":"Yoon","year":"2023","journal-title":"Clin Mol Hepatol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-024-10731-0","article-title":"Metabolic (dysfunction)-associated fatty liver disease metrics and contributions to liver research","volume":"18","author":"Suoh","year":"2024","journal-title":"Hepatol Int"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(24)00318-8","article-title":"Metabolic dysfunction-associated steatotic liver disease: heterogeneous pathomechanisms and effectiveness of metabolism-based treatment","volume":"13","author":"Stefan","year":"2025","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23280","article-title":"Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications","volume":"51","author":"Fabbrini","year":"2010","journal-title":"Hepatology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/s13098-022-00814-z","article-title":"NAFLD in normal weight individuals","volume":"14","author":"Distefano","year":"2022","journal-title":"Diabetol Metab syndrome"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.3390\/biomedicines9101346","article-title":"Non-alcoholic fatty liver disease in lean and non-obese individuals: current and future challenges","volume":"9","author":"Kuchay","year":"2021","journal-title":"Biomedicines"},{"key":"B11","doi-asserted-by":"publisher","first-page":"801","DOI":"10.3390\/diagnostics12040801","article-title":"Clinical and laboratory characteristics of normal weight and obese individuals with non-alcoholic fatty liver disease","volume":"12","author":"Trifan","year":"2022","journal-title":"Diagnostics"},{"key":"B12","doi-asserted-by":"publisher","first-page":"846","DOI":"10.4254\/wjh.v7.i6.846","article-title":"Non-alcoholic fatty liver disease: The diagnosis and management","volume":"7","author":"Abd El-Kader","year":"2015","journal-title":"World J Hepatol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1217249","article-title":"Lean nonalcoholic fatty liver disease and sarcopenia","volume":"14","author":"Chen","year":"2023","journal-title":"Front Endocrinol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(20)30077-7","article-title":"Global prevalence, incidence, and outcomes of non-obese or lean non-alcoholic fatty liver disease: a systematic review and meta-analysis","volume":"5","author":"Ye","year":"2020","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"502","DOI":"10.14218\/JCTH.2022.00204","article-title":"Nonalcoholic fatty liver disease in lean\/nonobese and obese individuals: a comprehensive review on prevalence, pathogenesis, clinical outcomes, and treatment","volume":"11","author":"Patel","year":"2022","journal-title":"J Clin Trans Hepatol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1053\/j.gastro.2022.06.023","article-title":"AGA clinical practice update: diagnosis and management of nonalcoholic fatty liver disease in lean individuals: expert review","volume":"163","author":"Long","year":"2022","journal-title":"Gastroenterology"},{"key":"B17","article-title":"Fatty liver disease: a practical guide for GPs","volume":"42","author":"Iser","year":"2013","journal-title":"Aust Family physician"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31021","article-title":"Obesity-associated improvements in metabolic profile through expansion of adipose tissue","volume":"117","author":"Kim","year":"2007","journal-title":"J Clin Invest"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1111\/eci.12519","article-title":"Adipose tissue and metabolic syndrome: too much, too little or neither","volume":"45","author":"Grundy","year":"2015","journal-title":"Eur J Clin Invest"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20896","article-title":"Adipokines in NASH: postprandial lipid metabolism as a link between adiponectin and liver disease","volume":"42","author":"Musso","year":"2005","journal-title":"Hepatology"},{"key":"B21","doi-asserted-by":"publisher","first-page":"726","DOI":"10.21037\/atm-20-3760","article-title":"Non-alcoholic fatty liver diseases: current challenges and future directions","volume":"9","author":"Roeb","year":"2021","journal-title":"Ann Trans Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"736","DOI":"10.3390\/medicina61040736","article-title":"Non-invasive tests as a replacement for liver biopsy in the assessment of MASLD","volume":"61","author":"Fr\u0105czek","year":"2025","journal-title":"Medicina"},{"key":"B23","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s43066-025-00419-x","article-title":"Serum Mac-2 binding protein glycosylation isomer as a biomarker for metabolic dysfunction associated steatotic liver disease","volume":"15","author":"Mansour","year":"2025","journal-title":"Egyptian Liver J"},{"key":"B24","doi-asserted-by":"publisher","first-page":"6","DOI":"10.2174\/0113892037315931240618085529","article-title":"Value of Mac-2 binding protein glycosylation isomer (M2BPGi) in assessing liver fibrosis in metabolic dysfunction-associated liver disease: A comprehensive review of its serum biomarker role","volume":"26","author":"Sotoudeheian","year":"2025","journal-title":"Curr Protein Pept Sci"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s40618-025-02636-y","article-title":"GDF15: An emerging disease target and biomarker of metabolic diseases","author":"Yang","year":"2025","journal-title":"J Endocrinological Invest"},{"key":"B26","doi-asserted-by":"publisher","first-page":"216","DOI":"10.14218\/JCTH.2016.00068","article-title":"Non-alcoholic fatty liver disease in lean subjects: characteristics and implications","volume":"5","author":"Kumar","year":"2017","journal-title":"J Clin Trans Hepatol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"638","DOI":"10.4254\/wjh.v7.i4.638","article-title":"Non-invasive methods for the diagnosis of nonalcoholic fatty liver disease","volume":"7","author":"Papagianni","year":"2015","journal-title":"World J Hepatol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"9","DOI":"10.2337\/dsi23-0010","article-title":"Understanding the burden of nonalcoholic fatty liver disease: time for action","volume":"37","author":"Younossi","year":"2024","journal-title":"Diabetes Spectr"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41366-023-01346-w","article-title":"Lean Indian patients with non-alcoholic fatty liver disease (NAFLD) have less metabolic risk factors but similar liver disease severity as non-lean patients with NAFLD","volume":"47","author":"De","year":"2023","journal-title":"Int J Obes"},{"key":"B30","doi-asserted-by":"publisher","first-page":"11","DOI":"10.21037\/tgh-23-31","article-title":"Genetic and epigenetic determinants of non-alcoholic fatty liver disease (NAFLD) in lean individuals: a systematic review","volume":"9","author":"Njei","year":"2024","journal-title":"Transl Gastroenterol Hepatol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1519","article-title":"Prevalence and profile of nonalcoholic fatty liver disease in lean adults: systematic review and meta-analysis","volume":"4","author":"Young","year":"2020","journal-title":"Hepatol Commun"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000004","article-title":"The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review","volume":"77","author":"Younossi","year":"2023","journal-title":"Hepatology"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2022.0239","article-title":"Forecasted 2040 global prevalence of nonalcoholic fatty liver disease using hierarchical bayesian approach","volume":"28","author":"Le","year":"2022","journal-title":"Clin Mol Hepatol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"S32","DOI":"10.3350\/cmh.2022.0365","article-title":"Global incidence and prevalence of nonalcoholic fatty liver disease","volume":"29","author":"Teng","year":"2023","journal-title":"Clin Mol Hepatol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1007\/s12072-025-10801-x","article-title":"Global prevalence, metabolic characteristics, and outcomes of lean-MAFLD: a systematic review and meta-analysis","volume":"10","author":"Cheah","year":"2025","journal-title":"Hepatol Int"},{"key":"B36","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s12986-025-00927-y","article-title":"Clinical characteristics of lean and non-lean non-alcoholic fatty liver disease: a cross-sectional study","volume":"22","author":"Xu","year":"2025","journal-title":"Nutr Metab (Lond)"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.16049","article-title":"Epidemiology and prevalence of lean nonalcoholic fatty liver disease and associated cirrhosis, hepatocellular carcinoma, and cardiovascular outcomes in the United States: a population-based study and review of literature","volume":"38","author":"Almomani","year":"2023","journal-title":"J Gastroenterol Hepatol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","article-title":"Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention","volume":"15","author":"Younossi","year":"2018","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2019.08.002","article-title":"Non-alcoholic fatty liver disease in lean individuals","volume":"1","author":"Albhaisi","year":"2019","journal-title":"JHEP Rep"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v16.i3.452","article-title":"Update in lean metabolic dysfunction-associated steatotic liver disease","volume":"16","author":"Sato-Espinoza","year":"2024","journal-title":"World J Hepatol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.5114\/amsad.2019.87122","article-title":"Comparison of clinical characteristics between lean and obese nonalcoholic fatty liver disease in the northeast Chinese population","volume":"4","author":"Li","year":"2019","journal-title":"Arch Med Sci Atheroscler Dis"},{"key":"B42","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1002\/hep4.1143","article-title":"Lean NAFLD: A not so benign condition","volume":"2","author":"Vanwagner","year":"2018","journal-title":"Hepatol Commun"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3390\/livers3030033","article-title":"Relationship between non-alcoholic fatty liver disease and visceral fat measured by imaging-based body composition analysis: a systematic review","volume":"3","author":"Seaw","year":"2023","journal-title":"Livers"},{"key":"B44","article-title":"Lean nonalcoholic steatohepatitis and nonalcoholic fatty liver disease","volume":"17","author":"Gunn","year":"2021","journal-title":"Gastroenterol Hepatol (N Y)"},{"key":"B45","doi-asserted-by":"crossref","DOI":"10.2147\/DMSO.S162157","article-title":"Subcutaneous to visceral fat ratio: a possible risk factor for metabolic syndrome and cardiovascular diseases","volume-title":"Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy","author":"Shafqat","year":"2018"},{"key":"B46","doi-asserted-by":"publisher","first-page":"102400","DOI":"10.1016\/j.jceh.2024.102400","article-title":"Central obesity is an independent determinant of advanced fibrosis in lean patients with nonalcoholic fatty liver disease","volume":"15","author":"De","year":"2025","journal-title":"J Clin Exp Hepatol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0000000000000317","article-title":"Lean, but not healthy: the \u2018metabolically obese, normal-weight\u2019phenotype","volume":"19","author":"Ding","year":"2016","journal-title":"Curr Opin Clin Nutr Metab Care"},{"key":"B48","doi-asserted-by":"publisher","first-page":"800","DOI":"10.3390\/nu9080800","article-title":"Dietary composition independent of weight loss in the management of non-alcoholic fatty liver disease","volume":"9","author":"Eslamparast","year":"2017","journal-title":"Nutrients"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2024.1398184","article-title":"Fruit and vegetable intake and the risk of non-alcoholic fatty liver disease: a meta-analysis of observational studies","volume":"11","author":"Wang","year":"2024","journal-title":"Front Nutr"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13391","article-title":"Short sleep duration and risk of nonalcoholic fatty liver disease: A systematic review and meta-analysis","volume":"31","author":"Wijarnpreecha","year":"2016","journal-title":"J Gastroenterol Hepatol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"101761","DOI":"10.1016\/j.aohep.2024.101761","article-title":"PNPLA3 and SAMM50 variants are associated with lean nonalcoholic fatty liver disease in Asian population","volume":"30","author":"Lu","year":"2025","journal-title":"Ann Hepatol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32491","article-title":"PNPLA3 rs738409 and risk of fibrosis in NAFLD: exploring mediation pathways through intermediate histological features","volume":"76","author":"Vilar-Gomez","year":"2022","journal-title":"Hepatology"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1822","article-title":"TM6SF2: a novel genetic player in nonalcoholic fatty liver and cardiovascular disease","volume":"6","author":"Luo","year":"2022","journal-title":"Hepatol Commun"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-025-04257-x","article-title":"Beyond obesity: lean metabolic dysfunction-associated steatohepatitis from unveiling molecular pathogenesis to therapeutic advancement","volume":"398","author":"Bhattacharya","year":"2025","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"70","DOI":"10.14218\/JCTH.2023.00252","article-title":"Unique genetic features of lean NAFLD: a review of mechanisms and clinical implications","volume":"12","author":"Tidwell","year":"2023","journal-title":"J Clin Trans Hepatol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1186\/s40001-024-01708-8","article-title":"Exploring the role of genetic variations in NAFLD: implications for disease pathogenesis and precision medicine approaches","volume":"29","author":"Mahmoudi","year":"2024","journal-title":"Eur J Med Res"},{"key":"B57","doi-asserted-by":"publisher","first-page":"91100","DOI":"10.4291\/wjgp.v15.i1.91100","article-title":"Prevalence and outcome of sarcopenia in non-alcoholic fatty liver disease","volume":"15","author":"Giri","year":"2024","journal-title":"World J Gastrointestinal Pathophysiology"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3390\/ijms11041509","article-title":"Oxidative stress, molecular inflammation and sarcopenia","volume":"11","author":"Meng","year":"2010","journal-title":"Int J Mol Sci"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.14309\/ctg.0000000000000326","article-title":"Nonalcoholic fatty liver disease in lean subjects: associations with metabolic dysregulation and cardiovascular risk\u2014a single-center cross-sectional study","volume":"12","author":"Semmler","year":"2021","journal-title":"Clin Trans Gastroenterol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2014.1798","article-title":"Elevated levels of alanine transaminase and triglycerides within normal limits are associated with fatty liver","volume":"8","author":"Tomizawa","year":"2014","journal-title":"Exp Ther Med"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12944-019-0986-7","article-title":"Triglycerides to high-density lipoprotein cholesterol ratio as a surrogate for nonalcoholic fatty liver disease: a cross-sectional study","volume":"18","author":"Fan","year":"2019","journal-title":"Lipids Health Dis"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.1089359","article-title":"The role of bile acid metabolism in the occurrence and development of NAFLD","volume":"9","author":"Bing","year":"2022","journal-title":"Front Mol Biosci"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30908","article-title":"Lean NAFLD: a distinct entity shaped by differential metabolic adaptation","volume":"71","author":"Chen","year":"2020","journal-title":"Hepatology"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2025.1673517","article-title":"Gut microbial signatures associated with the Indian lean MASLD phenotype","volume":"12","author":"Dey","year":"2025","journal-title":"Front Nutr"},{"key":"B65","doi-asserted-by":"publisher","first-page":"32002","DOI":"10.1038\/srep32002","article-title":"Altered fecal microbiota correlates with liver biochemistry in nonobese patients with non-alcoholic fatty liver disease","volume":"6","author":"Wang","year":"2016","journal-title":"Sci Rep"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.numecd.2017.10.014","article-title":"Gut microbiome composition in lean patients with NASH is associated with liver damage independent of caloric intake: A prospective pilot study","volume":"28","author":"Duarte","year":"2018","journal-title":"Nutr Metab Cardiovasc Dis"},{"key":"B67","doi-asserted-by":"publisher","first-page":"4982","DOI":"10.1038\/s41467-020-18754-5","article-title":"Distinct signatures of gut microbiome and metabolites associated with significant fibrosis in non-obese NAFLD","volume":"11","author":"Lee","year":"2020","journal-title":"Nat Commun"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22848","article-title":"Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease","volume":"49","author":"Miele","year":"2009","journal-title":"Hepatology"},{"key":"B69","doi-asserted-by":"publisher","first-page":"105135","DOI":"10.1016\/j.phrs.2020.105135","article-title":"Targeting gut barrier dysfunction with phytotherapies: Effective strategy against chronic diseases","volume":"161","author":"Dey","year":"2020","journal-title":"Pharmacol Res"},{"key":"B70","doi-asserted-by":"publisher","first-page":"243","DOI":"10.3390\/biology13040243","article-title":"Intestinal barrier dysfunction and gut microbiota in non-alcoholic fatty liver disease: assessment, mechanisms, and therapeutic considerations","volume":"13","author":"Long","year":"2024","journal-title":"Biology"},{"key":"B71","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/s41392-022-01073-0","article-title":"Trends in insulin resistance: insights into mechanisms and therapeutic strategy","volume":"7","author":"Li","year":"2022","journal-title":"Signal transduction targeted Ther"},{"key":"B72","doi-asserted-by":"publisher","first-page":"e13622","DOI":"10.1111\/eci13622","article-title":"Mitochondria, oxidative stress and nonalcoholic fatty liver disease: A complex relationship","volume":"52","author":"Karkucinska-Wieckowska","year":"2022","journal-title":"Eur J Clin Invest"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1148934","article-title":"Obesity, non-alcoholic fatty liver disease and hepatocellular carcinoma: current status and therapeutic targets","volume":"14","author":"Chen","year":"2023","journal-title":"Front Endocrinol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"4","DOI":"10.21037\/tgh-20-125","article-title":"Mitochondrial dysfunction in nonalcoholic fatty liver disease and alcohol related liver disease","volume":"6","author":"Prasun","year":"2021","journal-title":"Transl Gastroenterol Hepatol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1271","article-title":"Mitochondrial oxidative stress and antioxidants balance in fatty liver disease","volume":"2","author":"Garc\u00eda-Ruiz","year":"2018","journal-title":"Hepatol Commun"},{"key":"B76","doi-asserted-by":"publisher","first-page":"7405","DOI":"10.3390\/ijms25137405","article-title":"Exploring fibrosis pathophysiology in lean and obese metabolic-associated fatty liver disease: an in-depth comparison","volume":"25","author":"Veskovi\u0107","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B77","doi-asserted-by":"publisher","first-page":"200210","DOI":"10.1016\/j.hnm.2023.200210","article-title":"Visceral fat: A key mediator of NAFLD development and progression","volume":"33","author":"Bansal","year":"2023","journal-title":"Hum Nutr Metab"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01607","article-title":"Chronic adipose tissue inflammation linking obesity to insulin resistance and type 2 diabetes","volume":"10","author":"Zatterale","year":"2020","journal-title":"Front Physiol"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2023.2179106","article-title":"Adiponectin\u2013leptin ratio for the early detection of lean non-alcoholic fatty liver disease independent of insulin resistance","volume":"55","author":"Lu","year":"2023","journal-title":"Ann Med"},{"key":"B80","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/s44324-025-00066-1","article-title":"Mechanisms and implications of the gut microbial modulation of intestinal metabolic processes","volume":"3","author":"Jyoti","year":"2025","journal-title":"NPJ Metab Health Dis"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.14744\/hf.2020.2020.0018","article-title":"The clinical and histological characteristics of patients with biopsy-proven non-alcoholic fatty liver disease in the absence of insulin resistance","volume":"1","author":"Demirtas","year":"","journal-title":"Hepatol Forum"},{"key":"B82","doi-asserted-by":"publisher","first-page":"101288","DOI":"10.1016\/j.aohep.2024.101288","article-title":"Lean non-alcoholic fatty liver disease and the risk of all-cause mortality: an updated meta-analysis","volume":"29","author":"Wongtrakul","year":"2024","journal-title":"Ann Hepatol"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12016","article-title":"Nonalcoholic fatty liver disease: an emerging threat to obese and diabetic individuals","volume":"1281","author":"Masuoka","year":"2013","journal-title":"Ann N Y Acad Sci"},{"key":"B84","doi-asserted-by":"publisher","first-page":"e003066","DOI":"10.1136\/bmjdrc-2022-003066","article-title":"Non-obese or lean non-alcoholic fatty liver disease was associated with increased risk of cancer in patients with type 2 diabetes mellitus","volume":"11","author":"Chen","year":"2023","journal-title":"BMJ Open Diabetes Res Care"},{"key":"B85","doi-asserted-by":"publisher","first-page":"290","DOI":"10.5009\/gnl210084","article-title":"Cardiovascular risk is elevated in lean subjects with nonalcoholic fatty liver disease","volume":"16","author":"Kim","year":"2021","journal-title":"Gut liver"},{"key":"B86","doi-asserted-by":"publisher","first-page":"6514","DOI":"10.3748\/wjg.v26.i42.6514","article-title":"Nonalcoholic fatty liver disease in lean subjects: Prognosis, outcomes and management","volume":"26","author":"Chrysavgis","year":"2020","journal-title":"World J Gastroenterol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2021-326874","article-title":"Current therapies and new developments in NASH","volume":"71","author":"Dufour","year":"2022","journal-title":"Gut"},{"key":"B88","doi-asserted-by":"publisher","first-page":"3107","DOI":"10.3390\/ijms23063107","article-title":"SGLT-2 inhibitors in NAFLD: expanding their role beyond diabetes and cardioprotection","volume":"23","author":"Androutsakos","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B89","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.3390\/ijms24021703","article-title":"GLP-1 receptor agonists in non-alcoholic fatty liver disease: current evidence and future perspectives","volume":"24","author":"Nevola","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B90","article-title":"Nonalcoholic fatty liver disease: common questions and answers on diagnosis and management","volume":"102","author":"Westfall","year":"2020","journal-title":"Am Family physician"},{"key":"B91","doi-asserted-by":"publisher","first-page":"20219","DOI":"10.1038\/s41598-022-23729-1","article-title":"Fat mass index as a screening tool for the assessment of non-alcoholic fatty liver disease","volume":"12","author":"Zhang","year":"2022","journal-title":"Sci Rep"},{"key":"B92","first-page":"45","article-title":"Non-alcoholic fatty liver disease may develop in individuals with normal body mass index","volume":"25","author":"Margariti","year":"2012","journal-title":"Ann Gastroenterol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2021.10.032","article-title":"Visceral fat area is an independent risk factor for overweight or obese nonalcoholic fatty liver disease in potential living liver donors","volume":"54","author":"Lee","year":"2022","journal-title":"Transplant Proceedings: Elsevier"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1693123\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T13:43:56Z","timestamp":1760967836000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1693123\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,20]]},"references-count":93,"alternative-id":["10.3389\/fendo.2025.1693123"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1693123","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,20]]},"article-number":"1693123"}}