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This review explores the mechanistic basis and clinical implications of this axis. Molecularly, metabolically stressed hepatocytes release an altered hepatokine signature\u2014marked by reduced sex hormone-binding globulin (SHBG) and elevated fibroblast growth factor 21 (FGF21)\u2014along with pro-inflammatory cytokines (e.g., interleukin-1 beta (IL-1\u03b2), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-\u03b1)), which enter the systemic circulation. These factors may contribute to the impairment of Leydig cell steroidogenesis, the perturbation of blood\u2013testis barrier integrity, and the disruption of spermatogenesis. Conversely, testicular dysfunction and subsequent testosterone deficiency promote visceral adiposity, worsen insulin resistance and amplify chronic inflammation, thereby accelerating hepatic steatosis and fibrosis. Clinically, these molecular interactions manifest as mutually worsening of MASLD and HG. Thus, the liver\u2013testis axis establishes a framework that reveals the bidirectional crosstalk between hepatic metabolism and gonadal function, providing novel pathophysiological insights into these interconnected conditions.<\/jats:p>","DOI":"10.3390\/ijms27135873","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T02:11:57Z","timestamp":1782785517000},"page":"5873","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Liver\u2013Testis Axis: Molecular Mechanisms and Clinical Implications"],"prefix":"10.3390","volume":"27","author":[{"given":"Yapeng","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China"},{"name":"Graduate School of China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China"},{"name":"Graduate School of Hebei University of Chinese Medicine, Shijiazhuang 050091, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hede","family":"Zou","sequence":"additional","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4538-9606","authenticated-orcid":false,"given":"Wenkang","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayou","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","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","journal-title":"J. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1328","DOI":"10.1080\/00365521.2023.2220857","article-title":"Testosterone is lower in men with non-alcoholic fatty liver disease and alcohol-related cirrhosis and is associated with adverse clinical outcomes","volume":"58","author":"Apostolov","year":"2023","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"A292","DOI":"10.1210\/jendso\/bvab048.595","article-title":"Low Testosterone in Males May Warrant Liver Health Assessment and Intervention","volume":"5","author":"DelConte","year":"2021","journal-title":"J. Endocr. Soc."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zhao, J., Zhang, X., Li, Y., Yu, J., Chen, Z., Niu, Y., Ran, S., Wang, S., Ye, W., and Luo, Z. (2023). Interorgan communication with the liver: Novel mechanisms and therapeutic targets. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1314123"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.sxmr.2019.01.002","article-title":"Nonalcoholic Fatty Liver Disease, Male Sexual Dysfunction, and Infertility: Common Links, Common Problems","volume":"8","author":"Hawksworth","year":"2020","journal-title":"Sex. Med. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Qu, X., and Donnelly, R. (2020). Sex Hormone-Binding Globulin (SHBG) as an Early Biomarker and Therapeutic Target in Polycystic Ovary Syndrome. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218191"},{"key":"ref_7","first-page":"160","article-title":"Regulation of production and secretion of sex hormone-binding globulin in HepG2 cell cultures by hormones and growth factors","volume":"80","author":"Loukovaara","year":"1995","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Fodor Duric, L., Bel\u010di\u0107, V., Oberiter Korbar, A., \u0106urkovi\u0107, S., Vujicic, B., Gulin, T., Muslim, J., Gulin, M., Grgurevi\u0107, M., and Catic Cuti, E. (2024). The Role of SHBG as a Marker in Male Patients with Metabolic-Associated Fatty Liver Disease: Insights into Metabolic and Hormonal Status. J. Clin. Med., 13.","DOI":"10.3390\/jcm13247717"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"113","DOI":"10.5534\/wjmh.180055","article-title":"Metabolic Syndrome and Male Fertility","volume":"37","author":"Martins","year":"2019","journal-title":"World J. Men\u2019s Health"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.2337\/db23-0982","article-title":"Association Between Low Sex Hormone-Binding Globulin and Increased Risk of Type 2 Diabetes Is Mediated by Increased Visceral and Liver Fat: Results from Observational and Mendelian Randomization Analyses","volume":"73","author":"Stangl","year":"2024","journal-title":"Diabetes"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1055\/a-1778-4159","article-title":"FGF21: A Novel Regulator of Glucose and Lipid Metabolism and Whole-Body Energy Balance","volume":"54","year":"2022","journal-title":"Horm. Metab. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1210\/en.2014-1619","article-title":"The protective effect of FGF21 on diabetes-induced male germ cell apoptosis is associated with up-regulated testicular AKT and AMPK\/Sirt1\/PGC-1\u03b1 signaling","volume":"156","author":"Jiang","year":"2015","journal-title":"Endocrinology"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bourdon, G., Estienne, A., Chevaleyre, C., Ram\u00e9, C., Gu\u00e9rif, F., Brun, J.S., Vasseur, C., Fromont, G., Plotton, I., and Dufour-Rainfray, D. (2022). The Hepatokine FGF21 Increases the Human Spermatozoa Motility. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.775650"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1210\/endo-123-6-2935","article-title":"Fibroblast growth factor inhibits luteinizing hormone-stimulated androgen production by cultured rat testicular cells","volume":"123","author":"Fauser","year":"1988","journal-title":"Endocrinology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1055\/a-0879-2968","article-title":"Circulating FGF21 Levels in Human Health and Metabolic Disease","volume":"128","author":"Keuper","year":"2020","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1007\/BF03346393","article-title":"Male hypogonadism in cirrhosis and after liver transplantation","volume":"31","author":"Foresta","year":"2008","journal-title":"J. Endocrinol. Investig."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1111\/bph.15725","article-title":"Efruxifermin, a long-acting Fc-fusion FGF21 analogue, reduces body weight gain but does not increase sympathetic tone or urine volume in Sprague Dawley rats","volume":"179","author":"Tillman","year":"2022","journal-title":"Br. J. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.3390\/biomedicines13051260","article-title":"Chronic Inflammation and Immune Dysregulation in Metabolic-Dysfunction-Associated Steatotic Liver Disease Progression: From Steatosis to Hepatocellular Carcinoma","volume":"13","author":"Jee","year":"2025","journal-title":"Biomedicines"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1097\/MEG.0000000000000408","article-title":"Nonalcoholic fatty liver disease and alteration in semen quality and reproductive hormones","volume":"27","author":"Li","year":"2015","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"110339","DOI":"10.1016\/j.intimp.2023.110339","article-title":"Exenatide improves hypogonadism and attenuates inflammation in diabetic mice by modulating gut microbiota","volume":"120","author":"Chen","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/BF02738619","article-title":"Role of cytokines in testicular function","volume":"10","author":"Hales","year":"1999","journal-title":"Endocrine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1097\/00042737-200107000-00004","article-title":"Cytokines in the liver","volume":"13","author":"Ramadori","year":"2001","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Gong, J., Tu, W., Liu, J., and Tian, D. (2022). Hepatocytes: A key role in liver inflammation. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1083780"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"26631","DOI":"10.1038\/s41598-025-10192-x","article-title":"Hepatocyte FoxO1 depletion exacerbates hepatic inflammation in MASH by targeting cystathionine \u03b3-lyase","volume":"15","author":"Chen","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1002\/jemt.20704","article-title":"Cytokines and chemokines in testicular inflammation: A brief review","volume":"72","author":"Guazzone","year":"2009","journal-title":"Microsc. Res. Tech."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12958-018-0341-2","article-title":"The in vitro modulation of steroidogenesis by inflammatory cytokines and insulin in TM3 Leydig cells","volume":"16","author":"Leisegang","year":"2018","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/BF02801322","article-title":"Differential effects of tumor necrosis factor-alpha and interleukin-1 on 3 beta-hydroxysteroid dehydrogenase\/delta 5-->delta 4 isomerase expression in mouse Leydig cells","volume":"7","author":"Xiong","year":"1997","journal-title":"Endocrine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3519","DOI":"10.1210\/endo.136.8.7628389","article-title":"Tumor necrosis factor-alpha inhibition of 17 alpha-hydroxylase\/C17-20 lyase gene (Cyp17) expression","volume":"136","author":"Li","year":"1995","journal-title":"Endocrinology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/hep.28709","article-title":"Bile acids and nonalcoholic fatty liver disease: Molecular insights and therapeutic perspectives","volume":"65","author":"Arab","year":"2017","journal-title":"Hepatology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/s41392-024-01811-6","article-title":"Bile acid metabolism and signaling in health and disease: Molecular mechanisms and therapeutic targets","volume":"9","author":"Fleishman","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.stemcr.2017.05.036","article-title":"The Bile Acid Nuclear Receptor FXR\u03b1 Is a Critical Regulator of Mouse Germ Cell Fate","volume":"9","author":"Martinot","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"19468","DOI":"10.18632\/oncotarget.7153","article-title":"Bile acid-FXR\u03b1 pathways regulate male sexual maturation in mice","volume":"7","author":"Baptissart","year":"2016","journal-title":"Oncotarget"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.mam.2017.05.004","article-title":"Bile acids and male fertility: From mouse to human?","volume":"56","author":"Martinot","year":"2017","journal-title":"Mol. Asp. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"42182","DOI":"10.1038\/srep42182","article-title":"Bile acid homeostasis controls CAR signaling pathways in mouse testis through FXRalpha","volume":"7","author":"Martinot","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Holota, H., De Haze, A., Martinot, E., Monrose, M., Saru, J.P., Caira, F., Beaudoin, C., and Volle, D.H. (2022). Identification of the Role of TGR5 in the Regulation of Leydig Cell Homeostasis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232315398"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e2200626","DOI":"10.1002\/advs.202200626","article-title":"Identification of a Crosstalk among TGR5, GLIS2, and TP53 Signaling Pathways in the Control of Undifferentiated Germ Cell Homeostasis and Chemoresistance","volume":"9","author":"Thirouard","year":"2022","journal-title":"Adv. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1515\/mr-2024-0020","article-title":"Dysregulated bile acid homeostasis: Unveiling its role in metabolic diseases","volume":"4","author":"Wang","year":"2024","journal-title":"Med. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"108606","DOI":"10.4254\/wjh.v17.i8.108606","article-title":"Bile acids in metabolic dysfunction-associated steatotic liver disease","volume":"17","author":"Zerem","year":"2025","journal-title":"World J. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1053\/j.gastro.2013.05.042","article-title":"Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease","volume":"145","author":"Mudaliar","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/0005-2760(87)90081-6","article-title":"Deprivation and repletion of androgen in vivo modifies triacylglycerol synthesis by rat hepatocytes","volume":"921","author":"Elam","year":"1987","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"R25","DOI":"10.1530\/JOE-12-0455","article-title":"Testosterone: A metabolic hormone in health and disease","volume":"217","author":"Kelly","year":"2013","journal-title":"J. Endocrinol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.lfs.2014.06.007","article-title":"Testosterone suppresses the expression of regulatory enzymes of fatty acid synthesis and protects against hepatic steatosis in cholesterol-fed androgen deficient mice","volume":"109","author":"Kelly","year":"2014","journal-title":"Life Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"E366","DOI":"10.1152\/ajpendo.00124.2017","article-title":"Testosterone protects high-fat\/low-carbohydrate diet-induced nonalcoholic fatty liver disease in castrated male rats mainly via modulating endoplasmic reticulum stress","volume":"314","author":"Jia","year":"2018","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"294278","DOI":"10.1155\/2015\/294278","article-title":"Sex Hormones and Their Receptors Regulate Liver Energy Homeostasis","volume":"2015","author":"Shen","year":"2015","journal-title":"Int. J. Endocrinol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"754","DOI":"10.4254\/wjh.v14.i4.754","article-title":"Testosterone therapy reduces hepatic steatosis in men with type 2 diabetes and low serum testosterone concentrations","volume":"14","author":"Apostolov","year":"2022","journal-title":"World J. Hepatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1016\/j.dsx.2020.07.049","article-title":"Nonalcoholic fatty liver disease in males with low testosterone concentrations","volume":"14","author":"Polyzos","year":"2020","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e522","DOI":"10.1210\/clinem\/dgad586","article-title":"Noninvasive Indices of MASLD Are Associated with Hypogonadism in Male Patients with Type 2 Diabetes Mellitus","volume":"109","author":"Caretta","year":"2024","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1080\/2090598X.2021.1959261","article-title":"Testosterone treatment improves liver function and reduces cardiovascular risk: A long-term prospective study","volume":"19","author":"Yassin","year":"2021","journal-title":"Arab J. Urol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1080\/13685538.2020.1867094","article-title":"Long-term testosterone therapy improves liver parameters and steatosis in hypogonadal men: A prospective controlled registry study","volume":"23","author":"Yassin","year":"2020","journal-title":"Aging Male Off. J. Int. Soc. Study Aging Male"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/978-3-319-70178-3_12","article-title":"Role of Estrogens in the Regulation of Liver Lipid Metabolism","volume":"1043","author":"Palmisano","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1210\/jcem-40-3-367","article-title":"Aromatization of androgens by human abdominal and breast fat tissue","volume":"40","author":"Nimrod","year":"1975","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1210\/jcem-51-5-1128","article-title":"Enhanced conversion of androstenedione to estrogens in obese males","volume":"51","author":"Kley","year":"1980","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1038\/ijo.2017.50","article-title":"Hormone signaling and fatty liver in females: Analysis of estrogen receptor \u03b1 mutant mice","volume":"41","author":"Arao","year":"2017","journal-title":"Int. J. Obes."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.jsbmb.2007.05.029","article-title":"Estrogen and adiposity\u2014Utilizing models of aromatase deficiency to explore the relationship","volume":"106","author":"Jones","year":"2007","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"E1188","DOI":"10.1152\/ajpendo.00579.2013","article-title":"Estrogen signaling prevents diet-induced hepatic insulin resistance in male mice with obesity","volume":"306","author":"Zhu","year":"2014","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"388","DOI":"10.4274\/jcrpe.galenos.2019.2019.0027","article-title":"Clinical and Biochemical Phenotype of Adolescent Males with Gynecomastia","volume":"11","author":"Lorek","year":"2019","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.coemr.2020.03.002","article-title":"Puberty in patients with aromatase disorders","volume":"14","author":"Fukami","year":"2020","journal-title":"Curr. Opin. Endocr. Metab. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"41","DOI":"10.2169\/internalmedicine1962.26.41","article-title":"Gonadal function in male patients with alcoholic and non-alcoholic liver disease","volume":"26","author":"Kishimoto","year":"1987","journal-title":"Jpn. J. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1210\/jc.2004-2190","article-title":"Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men","volume":"90","author":"Pitteloud","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"582","DOI":"10.18632\/aging.100585","article-title":"Lipid-induced hepatic insulin resistance","volume":"5","author":"Galbo","year":"2013","journal-title":"Aging"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.cmet.2007.11.013","article-title":"Hepatic insulin resistance is sufficient to produce dyslipidemia and susceptibility to atherosclerosis","volume":"7","author":"Biddinger","year":"2008","journal-title":"Cell Metab."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.3390\/nu12071932","article-title":"Metformin Ameliorates Testicular Function and Spermatogenesis in Male Mice with High-Fat and High-Cholesterol Diet-Induced Obesity","volume":"12","author":"Liu","year":"2020","journal-title":"Nutrients"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/0026-0495(94)90202-X","article-title":"Decreased testosterone and dehydroepiandrosterone sulfate concentrations are associated with increased insulin and glucose concentrations in nondiabetic men","volume":"43","author":"Haffner","year":"1994","journal-title":"Metab. Clin. Exp."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1590\/S0004-27302009000800015","article-title":"Relationship between insulin and hypogonadism in men with metabolic syndrome","volume":"53","author":"Caldas","year":"2009","journal-title":"Arq. Bras. Endocrinol. Metabol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3164","DOI":"10.1172\/JCI119872","article-title":"Differential regulation of insulin receptor substrates-1 and -2 (IRS-1 and IRS-2) and phosphatidylinositol 3-kinase isoforms in liver and muscle of the obese diabetic (ob\/ob) mouse","volume":"100","author":"Kerouz","year":"1997","journal-title":"J. Clin. Investig."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.2174\/0929867324666170426142826","article-title":"Divergent Roles of IRS (Insulin Receptor Substrate) 1 and 2 in Liver and Skeletal Muscle","volume":"24","author":"Eckstein","year":"2017","journal-title":"Curr. Med. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.jcmgh.2018.10.016","article-title":"Resolving the Paradox of Hepatic Insulin Resistance","volume":"7","author":"Santoleri","year":"2019","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e3157","DOI":"10.1210\/clinem\/dgaa470","article-title":"Expression of the Insulin-like Growth Factor System in First- and Second-Trimester Human Embryonic and Fetal Gonads","volume":"105","author":"Mamsen","year":"2020","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Ipsa, E., Cruzat, V.F., Kagize, J.N., Yovich, J.L., and Keane, K.N. (2019). Growth Hormone and Insulin-Like Growth Factor Action in Reproductive Tissues. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00777"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"8837","DOI":"10.1074\/jbc.M709221200","article-title":"Steroidogenic Activity of StAR Requires Contact with Mitochondrial VDAC1 and Phosphate Carrier Protein*","volume":"283","author":"Bose","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1093\/biolreprod\/78.s1.200b","article-title":"The Differential Regulation of STAR-Mediated Steroidogenesis by Type I and Type II PKA","volume":"78","author":"Dyson","year":"2008","journal-title":"Biol. Reprod."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s10735-025-10671-5","article-title":"A Review on the Effects of Atrazine on Male Rat Reproductive System Cytoarchitecture, Steroidogenesis and Oxidative Pathway","volume":"57","author":"Oliveira","year":"2026","journal-title":"J. Mol. Histol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"5036","DOI":"10.1210\/en.2009-0771","article-title":"Convergence of 3\u2032,5\u2032-cyclic adenosine 5\u2032-monophosphate\/protein kinase A and glycogen synthase kinase-3beta\/beta-catenin signaling in corpus luteum progesterone synthesis","volume":"150","author":"Roy","year":"2009","journal-title":"Endocrinology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"641","DOI":"10.3390\/medicina58050641","article-title":"Chronic Inflammation-A Link between Nonalcoholic Fatty Liver Disease (NAFLD) and Dysfunctional Adipose Tissue","volume":"58","author":"Petrescu","year":"2022","journal-title":"Medicina"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.3390\/antiox10111834","article-title":"The Mechanisms and Management of Age-Related Oxidative Stress in Male Hypogonadism Associated with Non-communicable Chronic Disease","volume":"10","author":"Leisegang","year":"2021","journal-title":"Antioxidants"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1385\/ENDO:25:3:265","article-title":"Bacterial endotoxin lipopolysaccharide and reactive oxygen species inhibit Leydig cell steroidogenesis via perturbation of mitochondria","volume":"25","author":"Allen","year":"2004","journal-title":"Endocrine"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Ramos-Tovar, E., and Muriel, P. (2020). Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the Liver. Antioxidants, 9.","DOI":"10.3390\/antiox9121279"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1111\/cen.14930","article-title":"The Association between Inflammation, Testosterone and SHBG in men: A cross-sectional Multi-Ethnic Study of Atherosclerosis","volume":"99","author":"Osmancevic","year":"2023","journal-title":"Clin. Endocrinol."},{"key":"ref_79","first-page":"e14526","article-title":"The correlation between testosterone, inflammation and cytokine status in type-2 diabetes men","volume":"54","author":"Nakhleh","year":"2022","journal-title":"Andrologia"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Li, Y., Su, Y., Zhou, T., Hu, Z., Wei, J., Wang, W., Liu, C., Zhang, H., and Zhao, K. (2019). Activation of the NLRP3 Inflammasome Pathway by Prokineticin 2 in Testicular Macrophages of Uropathogenic Escherichia coli- Induced Orchitis. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01872"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1530\/REP-18-0111","article-title":"NLRP3 in somatic non-immune cells of rodent and primate testes","volume":"156","author":"Walenta","year":"2018","journal-title":"Reproduction"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.4049\/jimmunol.1202733","article-title":"Histones Activate the NLRP3 Inflammasome in Kupffer Cells during Sterile Inflammatory Liver Injury","volume":"191","author":"Huang","year":"2013","journal-title":"J. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"8277","DOI":"10.2147\/JIR.S532908","article-title":"NLRP3 Inflammasome Activation in Liver Disorders: From Molecular Pathways to Therapeutic Strategies","volume":"18","author":"Ma","year":"2025","journal-title":"J. Inflamm. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.molmed.2018.03.005","article-title":"IL-1 Family Cytokine Pathways Underlying NAFLD: Towards New Treatment Strategies","volume":"24","author":"Mirea","year":"2018","journal-title":"Trends Mol. Med."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Venditti, M., Romano, M.Z., Boccella, S., Haddadi, A., Biasi, A., Maione, S., and Minucci, S. (2024). Type 1 diabetes impairs the activity of rat testicular somatic and germ cells through NRF2\/NLRP3 pathway-mediated oxidative stress. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1399256"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s41232-022-00203-z","article-title":"Diet-induced obesity impairs spermatogenesis: The critical role of NLRP3 in Sertoli cells","volume":"42","author":"Mu","year":"2022","journal-title":"Inflamm. Regen."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Tang, Z., and Zheng, Y. (2025). Prepubertal Diabetes Stagnates Testicular Development by Skewing Autophagy Homeostasis in Leydig Cells. Cells, 14.","DOI":"10.3390\/cells14171376"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"44937","DOI":"10.1021\/acsomega.5c02017","article-title":"Overactivation of PERK-Mediated Endoplasmic Reticulum Stress-Induced Testis Damage in Chronically Stressed Mice","volume":"10","author":"Peng","year":"2025","journal-title":"ACS Omega"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"109735","DOI":"10.1016\/j.steroids.2025.109735","article-title":"Endoplasmic reticulum stress and steroidogenic dysfunction in Leydig cells: Molecular mechanisms of UPR-mediated testosterone regulation","volume":"226","author":"Martin","year":"2026","journal-title":"Steroids"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1210\/en.2010-1036","article-title":"Constitutive role for IRE1\u03b1-XBP1 signaling pathway in the insulin-mediated hepatic lipogenic program","volume":"152","author":"Ning","year":"2011","journal-title":"Endocrinology"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Li, J., Jiang, Z., Luo, W., Tang, K., Liang, D., Luo, X., Liu, L., Long, Z., Huang, H., and Chen, W. (2026). Research progress on the multidimensional mechanisms underlying impaired spermatogenesis induced by pathological microenvironment remodeling in chronic prostatitis. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1793156"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2361202","DOI":"10.1080\/21688370.2024.2361202","article-title":"The role of reactive oxygen species in the regulation of the blood-brain barrier","volume":"13","author":"Shuvalova","year":"2025","journal-title":"Tissue Barriers"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1007\/s00018-017-2687-6","article-title":"Microcystin-leucine-arginine causes blood-testis barrier disruption and degradation of occludin mediated by matrix metalloproteinase-8","volume":"75","author":"Chen","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"102886","DOI":"10.1016\/j.redox.2023.102886","article-title":"Nickel induces blood-testis barrier damage through ROS-mediated p38 MAPK pathways in mice","volume":"67","author":"Zeng","year":"2023","journal-title":"Redox Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"423","DOI":"10.3390\/biomedicines14020423","article-title":"Inflammation-Driven Remodeling of the Blood\u2013Testis Barrier: Roles of Junctional Complexes, Actin Dynamics, and Kinase Signaling","volume":"14","author":"Nagy","year":"2026","journal-title":"Biomedicines"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"17","DOI":"10.18502\/ijrm.v23i1.18187","article-title":"Interlinkage between inflammation, oxidative stress, and endoplasmic reticulum stress in bisphenols-induced testicular steroidogenesis disturbance: A mini review","volume":"23","year":"2025","journal-title":"Int. J. Reprod. Biomed."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Zhan, M.-W., Zhou, M.-H., Zhao, B.-B., Bao, X.-J., Chen, Y., and Zhu, J. (2025). Testicular immunosenescence: A key player in age-related spermatogenic decline. Front. Cell Dev. Biol., 13, Erratum in Front. Cell Dev. Biol.\u00a02025, 13, 1687852.","DOI":"10.3389\/fcell.2025.1669826"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.2147\/DMSO.S511436","article-title":"Lipotoxicity: A New Perspective in Type 2 Diabetes Mellitus","volume":"18","author":"Chen","year":"2025","journal-title":"Diabetes Metab. Syndr. Obes. Targets Ther."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.tem.2012.04.005","article-title":"Role of ceramides in nonalcoholic fatty liver disease","volume":"23","author":"Pagadala","year":"2012","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Hajduch, E., Lachkar, F., Ferr\u00e9, P., and Foufelle, F. (2021). Roles of Ceramides in Non-Alcoholic Fatty Liver Disease. J. Clin. Med., 10.","DOI":"10.3390\/jcm10040792"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"4763","DOI":"10.1210\/en.2003-0569","article-title":"Intratesticular delivery of tumor necrosis factor-alpha and ceramide directly abrogates steroidogenic acute regulatory protein expression and Leydig cell steroidogenesis in adult rats","volume":"144","author":"Morales","year":"2003","journal-title":"Endocrinology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/s43587-024-00614-2","article-title":"Targeting dysregulated phago-\/auto-lysosomes in Sertoli cells to ameliorate late-onset hypogonadism","volume":"4","author":"Deng","year":"2024","journal-title":"Nat. Aging"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Brankovi\u0107, M., Jovanovi\u0107, I., Duki\u0107, M., Radonji\u0107, T., Opri\u0107, S., Kla\u0161nja, S., and Zdravkovi\u0107, M. (2022). Lipotoxicity as the Leading Cause of Non-Alcoholic Steatohepatitis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23095146"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"12561","DOI":"10.1038\/s41598-021-92008-2","article-title":"Fatty acids suppress the steroidogenesis of the MA-10 mouse Leydig cell line by downregulating CYP11A1 and inhibiting late-stage autophagy","volume":"11","author":"Huang","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/j.cmet.2012.03.005","article-title":"Diacylglycerol Activation of Protein Kinase C\u03b5; and Hepatic Insulin Resistance","volume":"15","author":"Jornayvaz","year":"2012","journal-title":"Cell Metab."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1172\/JCI34275","article-title":"Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: Lessons from genetically engineered mice","volume":"118","author":"Postic","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1172\/JCI200422230","article-title":"PKC-theta knockout mice are protected from fat-induced insulin resistance","volume":"114","author":"Kim","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"S9","DOI":"10.2337\/db06-S002","article-title":"Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction","volume":"55","author":"Morino","year":"2006","journal-title":"Diabetes"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/S0006-291X(03)00449-2","article-title":"Saturated free fatty acids, palmitic acid and stearic acid, induce apoptosis by stimulation of ceramide generation in rat testicular Leydig cell","volume":"303","author":"Lu","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0960-0760(00)00188-6","article-title":"Possible involvement of ceramide in the regulation of rat Leydig cell function","volume":"75","author":"Meroni","year":"2000","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1007\/978-1-4020-8831-5_15","article-title":"Multiple roles for sphingolipids in steroid hormone biosynthesis","volume":"49","author":"Lucki","year":"2008","journal-title":"Sub-Cell. Biochem."},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Venugopal, S., Galano, M., Chan, R., Sanyal, E., Issop, L., Lee, S., Taylor, L., Kaur, P., Daly, E., and Papadopoulos, V. (2021). Dynamic Remodeling of Membranes and Their Lipids during Acute Hormone-Induced Steroidogenesis in MA-10 Mouse Leydig Tumor Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052554"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"11369","DOI":"10.1074\/jbc.272.17.11369","article-title":"Direct Effect of Ceramide on the Mitochondrial Electron Transport Chain Leads to Generation of Reactive Oxygen Species: ROLE OF MITOCHONDRIAL GLUTATHIONE*","volume":"272","author":"Colell","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Valenzuela-Ahumada, L.A., Mercado-G\u00f3mez, O.F., Viveros-Contreras, R., Guevara-Guzm\u00e1n, R., and Camacho-Morales, A. (2025). Fasting the mitochondria to prevent neurodegeneration: The role of ceramides. Front. Neurosci., 19.","DOI":"10.3389\/fnins.2025.1602149"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Diaz-Vegas, A., Madsen, S., Cooke, K.C., Carroll, L., Khor, J.X.Y., Turner, N., Lim, X.Y., Astore, M.A., Morris, J., and Don, A. (2023). Mitochondrial electron transport chain, ceramide and Coenzyme Q are linked in a pathway that drives insulin resistance in skeletal muscle. bioRxiv Prepr. Serv. Biol.","DOI":"10.7554\/eLife.87340.2"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2882","DOI":"10.1210\/en.2002-0090","article-title":"Reactive Oxygen Disrupts Mitochondria in MA-10 Tumor Leydig Cells and Inhibits Steroidogenic Acute Regulatory (StAR) Protein and Steroidogenesis","volume":"144","author":"Diemer","year":"2003","journal-title":"Endocrinology"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/S0039-128X(99)00013-6","article-title":"Ceramide increases steroid hormone production in MA-10 Leydig cells","volume":"64","author":"Kwun","year":"1999","journal-title":"Steroids"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.3349\/ymj.2015.56.6.1590","article-title":"The Role of Foxo3 in Leydig Cells","volume":"56","author":"Choi","year":"2015","journal-title":"Yonsei Med. J."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1091\/mbc.e09-09-0795","article-title":"Protein phosphatase 2A reactivates FOXO3a through a dynamic interplay with 14-3-3 and AKT","volume":"21","author":"Singh","year":"2010","journal-title":"Mol. Biol. Cell"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"102380","DOI":"10.1016\/j.redox.2022.102380","article-title":"Protein palmitoylation-mediated palmitic acid sensing causes blood-testis barrier damage via inducing ER stress","volume":"54","author":"Ge","year":"2022","journal-title":"Redox Biol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1093\/humrep\/deu011","article-title":"Environmental toxicants perturb human Sertoli cell adhesive function via changes in F-actin organization mediated by actin regulatory proteins","volume":"29","author":"Xiao","year":"2014","journal-title":"Hum. Reprod."},{"key":"ref_122","first-page":"214","article-title":"Protective and therapeutic role of melatonin against tunicamycin-induced ER stress in testicular tissue of rats","volume":"25","author":"Tatar","year":"2022","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_123","first-page":"101309","article-title":"The Cardiohepatic Axis in Metabolic Disease: Liver to Heart","volume":"10","author":"Hakeem","year":"2025","journal-title":"Basic Transl. Sci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.jhep.2019.10.003","article-title":"The gut-liver axis in liver disease: Pathophysiological basis for therapy","volume":"72","author":"Albillos","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/nrendo.2017.56","article-title":"Hepatokines: Linking nonalcoholic fatty liver disease and insulin resistance","volume":"13","author":"Meex","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"4260","DOI":"10.1038\/srep04260","article-title":"Interleukin-6 disrupts blood-testis barrier through inhibiting protein degradation or activating phosphorylated ERK in Sertoli cells","volume":"4","author":"Zhang","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"4254","DOI":"10.1210\/jc.2007-0454","article-title":"Acute sex steroid withdrawal reduces insulin sensitivity in healthy men with idiopathic hypogonadotropic hypogonadism","volume":"92","author":"Yialamas","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/j.bbadis.2016.11.010","article-title":"Mitochondrial dysfunction and oxidative stress in metabolic disorders\u2014A step towards mitochondria based therapeutic strategies","volume":"1863","author":"Bhatti","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s12943-025-02407-6","article-title":"Metabolic checkpoints in immune cell reprogramming: Rewiring immunometabolism for cancer therapy","volume":"24","author":"Lv","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.exphem.2020.01.011","article-title":"Clonal hematopoiesis and inflammation: Partners in leukemogenesis and comorbidity","volume":"83","author":"Cook","year":"2020","journal-title":"Exp. Hematol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5873\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T10:16:59Z","timestamp":1783592219000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5873"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,29]]},"references-count":130,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27135873"],"URL":"https:\/\/doi.org\/10.3390\/ijms27135873","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,29]]}}}