{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:36:33Z","timestamp":1792013793214,"version":"4.4.0"},"reference-count":54,"publisher":"American Diabetes Association","issue":"2","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["908952"],"award-info":[{"award-number":["908952"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"crossref","award":["9-22-PDFPM-01"],"award-info":[{"award-number":["9-22-PDFPM-01"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH","award":["1 T32 HL160520"],"award-info":[{"award-number":["1 T32 HL160520"]}]},{"name":"NIH","award":["R01 DK121140"],"award-info":[{"award-number":["R01 DK121140"]}]},{"name":"NIH","award":["R01 DK121844"],"award-info":[{"award-number":["R01 DK121844"]}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:p>Excessive adiposity in obesity is a significant risk factor for development of type 2 diabetes (T2D), nonalcoholic fatty liver disease, and other cardiometabolic diseases. An unhealthy expansion of adipose tissue (AT) results in reduced adipogenesis, increased adipocyte hypertrophy, adipocyte hypoxia, chronic low-grade inflammation, increased macrophage infiltration, and insulin resistance. This ultimately culminates in AT dysfunction characterized by decreased secretion of antidiabetic adipokines such as adiponectin and adipsin and increased secretion of proinflammatory prodiabetic adipokines including RBP4 and resistin. This imbalance in adipokine secretion alters the physiological state of AT communication with target organs including pancreatic \u03b2-cells, heart, and liver. In the pancreatic \u03b2-cells, adipokines are known to have a direct effect on insulin secretion, gene expression, cell death, and\/or dedifferentiation. For instance, impaired secretion of adipsin, which promotes insulin secretion and \u03b2-cell identity, results in \u03b2-cell failure and T2D, thus presenting a potential druggable target to improve and\/or preserve \u03b2-cell function. The cardiac tissue is affected by both the classic white AT\u2013secreted adipokines and the newly recognized brown AT (BAT)-secreted BATokines or lipokines that alter lipid deposition and ventricular function. In the liver, adipokines affect hepatic gluconeogenesis, lipid accumulation, and insulin sensitivity, underscoring the importance of adipose-liver communication in the pathogenesis of nonalcoholic fatty liver disease. In this perspective, we outline what is currently known about the effects of individual adipokines on pancreatic \u03b2-cells, liver, and the heart.<\/jats:p>","DOI":"10.2337\/dbi23-0005","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T15:08:15Z","timestamp":1705676895000},"page":"169-177","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":84,"title":["Adipose Signals Regulating Distal Organ Health and Disease"],"prefix":"10.2337","volume":"73","author":[{"given":"Ankit","family":"Gilani","sequence":"first","affiliation":[{"name":"Weill Center for Metabolic Health, Cardiovascular Research Institute, Department of Medicine, Weill Cornell Medicine, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Stoll","sequence":"additional","affiliation":[{"name":"Weill Center for Metabolic Health, Cardiovascular Research Institute, Department of Medicine, Weill Cornell Medicine, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin A.","family":"Homan","sequence":"additional","affiliation":[{"name":"Weill Center for Metabolic Health, Cardiovascular Research Institute, Department of Medicine, Weill Cornell Medicine, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0244-1670","authenticated-orcid":false,"given":"James C.","family":"Lo","sequence":"additional","affiliation":[{"name":"Weill Center for Metabolic Health, Cardiovascular Research Institute, Department of Medicine, Weill Cornell Medicine, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2024,1,19]]},"reference":[{"key":"2024011920081329900_B1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S2213-8587(19)30026-9","article-title":"The obesity transition: stages of the global epidemic","volume":"7","author":"Jaacks","year":"2019","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2024011920081329900_B2","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1126\/science.3299705","article-title":"Adipsin: a circulating serine protease homolog secreted by adipose tissue and sciatic nerve","volume":"237","author":"Cook","year":"1987","journal-title":"Science"},{"key":"2024011920081329900_B3","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.cell.2014.06.005","article-title":"Adipsin is an adipokine that improves \u03b2 cell function in diabetes","volume":"158","author":"Lo","year":"2014","journal-title":"Cell"},{"key":"2024011920081329900_B4","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1038\/s41591-019-0610-4","article-title":"Adipsin preserves beta cells in diabetic mice and associates with protection from type 2 diabetes in humans","volume":"25","author":"G\u00f3mez-Banoy","year":"2019","journal-title":"Nat Med"},{"key":"2024011920081329900_B5","doi-asserted-by":"crossref","first-page":"2346","DOI":"10.2337\/db15-0318","article-title":"Brown and beige fat: molecular parts of a thermogenic machine","volume":"64","author":"Cohen","year":"2015","journal-title":"Diabetes"},{"key":"2024011920081329900_B6","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1038\/s42255-020-00301-7","article-title":"Perivascular mesenchymal cells control adipose-tissue macrophage accrual in obesity","volume":"2","author":"Shan","year":"2020","journal-title":"Nat Metab"},{"key":"2024011920081329900_B7","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1016\/j.cmet.2021.09.009","article-title":"Hyperglycemia in acute COVID-19 is characterized by insulin resistance and adipose tissue infectivity by SARS-CoV-2","volume":"33","author":"Reiterer","year":"2021","journal-title":"Cell Metab"},{"key":"2024011920081329900_B8","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1006\/bbrc.1996.1059","article-title":"Leptin receptors expressed on pancreatic beta-cells","volume":"224","author":"Kieffer","year":"1996","journal-title":"Biochem Biophys Res Commun"},{"key":"2024011920081329900_B9","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.bbrc.2003.11.042","article-title":"Expression of adiponectin receptors in pancreatic beta cells","volume":"312","author":"Kharroubi","year":"2003","journal-title":"Biochem Biophys Res Commun"},{"key":"2024011920081329900_B10","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1126\/science.3299706","article-title":"Spiegelman BM. Severely impaired adipsin expression in genetic and acquired obesity","volume":"237","author":"Flier","year":"1987","journal-title":"Science"},{"key":"2024011920081329900_B11","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.1172\/JCI119818","article-title":"Leptin rapidly suppresses insulin release from insulinoma cells, rat and human islets and, in\u00a0vivo, in mice","volume":"100","author":"Kulkarni","year":"1997","journal-title":"J Clin Invest"},{"key":"2024011920081329900_B12","first-page":"585","article-title":"Restoration of Lepr in \u03b2 cells of Lepr null mice does not prevent hyperinsulinemia and hyperglycemia. Mol Metab","volume":"6","author":"D\u2019souza","year":"2017"},{"key":"2024011920081329900_B13","doi-asserted-by":"crossref","first-page":"33623","DOI":"10.1074\/jbc.M109.085084","article-title":"Adiponectin-induced ERK and Akt phosphorylation protects against pancreatic beta cell apoptosis and increases insulin gene expression and secretion","volume":"285","author":"Wijesekara","year":"2010","journal-title":"J Biol Chem"},{"key":"2024011920081329900_B14","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1042\/CS20190523","article-title":"Adipokines as key players in \u03b2 cell function and failure","volume":"133","author":"G\u00f3mez-Banoy","year":"2019","journal-title":"Clin Sci (Lond)"},{"key":"2024011920081329900_B15","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/35053000","article-title":"The hormone resistin links obesity to diabetes","volume":"409","author":"Steppan","year":"2001","journal-title":"Nature"},{"key":"2024011920081329900_B16","first-page":"1046","author":"Nakata"},{"key":"2024011920081329900_B17","first-page":"3273","author":"Brown"},{"key":"2024011920081329900_B18","doi-asserted-by":"crossref","first-page":"246","DOI":"10.4161\/isl.3.5.16427","article-title":"Diabetes mellitus is associated with an increased expression of resistin in human pancreatic islet cells","volume":"3","author":"Al-Salam","year":"2011","journal-title":"Islets"},{"key":"2024011920081329900_B19","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.cmet.2007.09.003","article-title":"Nampt\/PBEF\/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme","volume":"6","author":"Revollo","year":"2007","journal-title":"Cell Metab"},{"key":"2024011920081329900_B20","doi-asserted-by":"crossref","first-page":"3083","DOI":"10.1007\/s00125-011-2288-0","article-title":"Nicotinamide mononucleotide protects against pro-inflammatory cytokine-mediated impairment of mouse islet function","volume":"54","author":"Caton","year":"2011","journal-title":"Diabetologia"},{"key":"2024011920081329900_B21","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.molmet.2014.02.005","article-title":"Identification of fatty acid binding protein 4 as an adipokine that regulates insulin secretion during obesity","volume":"3","author":"Wu","year":"2014","journal-title":"Mol Metab"},{"key":"2024011920081329900_B22","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/s41586-021-04137-3","article-title":"A hormone complex of FABP4 and nucleoside kinases regulates islet function","volume":"600","author":"Prentice","year":"2021","journal-title":"Nature"},{"key":"2024011920081329900_B23","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1210\/en.2014-1631","article-title":"Pancreatic islet APJ deletion reduces islet density and glucose tolerance in mice","volume":"156","author":"Han","year":"2015","journal-title":"Endocrinology"},{"key":"2024011920081329900_B24","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1007\/s00018-013-1258-8","article-title":"Vaspin inhibits kallikrein 7 by serpin mechanism","volume":"70","author":"Heiker","year":"2013","journal-title":"Cell Mol Life Sci"},{"key":"2024011920081329900_B25","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/s41591-020-1126-7","article-title":"Brown adipose tissue is associated with cardiometabolic health","volume":"27","author":"Becher","year":"2021","journal-title":"Nat Med"},{"key":"2024011920081329900_B26","doi-asserted-by":"crossref","first-page":"840866","DOI":"10.3389\/fcell.2022.840866","article-title":"Associations of visceral adipose tissue, circulating protein biomarkers, and risk of cardiovascular diseases: a Mendelian randomization analysis","volume":"10","author":"Huang","year":"2022","journal-title":"Front Cell Dev Biol"},{"key":"2024011920081329900_B27","doi-asserted-by":"crossref","first-page":"31","DOI":"10.5507\/bp.2017.002","article-title":"Adipokines and cardiovascular disease: a comprehensive review","volume":"161","author":"Smekal","year":"2017","journal-title":"Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub"},{"key":"2024011920081329900_B28","first-page":"18","article-title":"Pathophysiological role of major adipokines in atrial fibrillation","volume":"22","author":"Rafaqat","year":"2021"},{"key":"2024011920081329900_B29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s13679-021-00465-7","article-title":"Batokines: mediators of inter-tissue communication (a mini-review)","volume":"11","author":"Yang","year":"2022","journal-title":"Curr Obes Rep"},{"key":"2024011920081329900_B30","doi-asserted-by":"crossref","first-page":"2931","DOI":"10.1097\/CM9.0000000000001890","article-title":"The role of FGF21 in the pathogenesis of cardiovascular disease","volume":"134","author":"Zhang","year":"2021","journal-title":"Chin Med J (Engl)"},{"key":"2024011920081329900_B31","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1186\/s12933-022-01643-0","article-title":"Neuregulin-4 attenuates diabetic cardiomyopathy by regulating autophagy via the AMPK\/mTOR signalling pathway","volume":"21","author":"Wang","year":"2022","journal-title":"Cardiovasc Diabetol"},{"key":"2024011920081329900_B32","doi-asserted-by":"crossref","first-page":"8197","DOI":"10.7150\/thno.43968","article-title":"Brown adipose tissue-derived exosomes mitigate the metabolic syndrome in high fat diet mice","volume":"10","author":"Zhou","year":"2020","journal-title":"Theranostics"},{"key":"2024011920081329900_B33","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1161\/CIRCRESAHA.121.320470","article-title":"Brown adipocyte ADRB3 mediates cardioprotection via suppressing exosomal iNOS","volume":"131","author":"Lin","year":"2022","journal-title":"Circ Res"},{"key":"2024011920081329900_B34","doi-asserted-by":"crossref","first-page":"20","DOI":"10.14797\/mdcj-13-1-20","article-title":"Epicardial fat in the maintenance of cardiovascular health","volume":"13","author":"Wu","year":"2017","journal-title":"Methodist DeBakey Cardiovasc J"},{"key":"2024011920081329900_B35","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1016\/j.jacc.2021.08.037","article-title":"Modulation of cardiac arrhythmogenesis by epicardial adipose tissue: JACC\u00a0state-of-the-art\u00a0review","volume":"78","author":"Ernault","year":"2021","journal-title":"J Am Coll Cardiol"},{"key":"2024011920081329900_B36","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.7150\/ijbs.36427","article-title":"Exosomes in coronary artery disease","volume":"15","author":"Gao","year":"2019","journal-title":"Int J Biol Sci"},{"key":"2024011920081329900_B37","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1053\/j.gastro.2019.11.312","article-title":"MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease","volume":"158","author":"Eslam","year":"2020","journal-title":"Gastroenterology"},{"key":"2024011920081329900_B38","doi-asserted-by":"crossref","first-page":"4138","DOI":"10.1172\/JCI127092","article-title":"PAHSAs enhance hepatic and systemic insulin sensitivity through direct and indirect mechanisms","volume":"129","author":"Zhou","year":"2019","journal-title":"J Clin Invest"},{"key":"2024011920081329900_B39","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.cmet.2014.05.005","article-title":"Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling","volume":"20","author":"Wernstedt Asterholm","year":"2014","journal-title":"Cell Metab"},{"key":"2024011920081329900_B40","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1002\/hep.23046","article-title":"Adipokines in liver diseases","volume":"50","author":"Marra","year":"2009","journal-title":"Hepatology"},{"key":"2024011920081329900_B41","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nm.2277","article-title":"Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin","volume":"17","author":"Holland","year":"2011","journal-title":"Nat Med"},{"key":"2024011920081329900_B42","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1111\/liv.12757","article-title":"Secreted frizzled-related protein 5 (Sfrp5) decreases hepatic stellate cell activation and liver fibrosis","volume":"35","author":"Chatani","year":"2015","journal-title":"Liver Int"},{"key":"2024011920081329900_B43","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.cell.2016.02.063","article-title":"Asprosin, a fasting-induced glucogenic protein hormone","volume":"165","author":"Romere","year":"2016","journal-title":"Cell"},{"key":"2024011920081329900_B44","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1530\/JOE-20-0503","article-title":"Novel adipokine asprosin modulates browning and adipogenesis in white adipose tissue","volume":"249","author":"Miao","year":"2021","journal-title":"J Endocrinol"},{"key":"2024011920081329900_B45","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.cmet.2019.02.004","article-title":"Case reports of pre-clinical replication studies in metabolism and diabetes","volume":"29","author":"von Herrath","year":"2019","journal-title":"Cell Metab"},{"key":"2024011920081329900_B46","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.cell.2014.06.005","article-title":"Adipsin is an adipokine that improves \u03b2 cell function in diabetes","volume":"158","author":"Lo","year":"2014","journal-title":"Cell"},{"key":"2024011920081329900_B47","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1002\/hep.28659","article-title":"Adipocyte-specific overexpression of retinol-binding protein 4 causes hepatic steatosis in mice","volume":"64","author":"Lee","year":"2016","journal-title":"Hepatology"},{"key":"2024011920081329900_B48","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/nature21365","article-title":"Adipose-derived circulating miRNAs regulate gene expression in other tissues","volume":"542","author":"Thomou","year":"2017","journal-title":"Nature"},{"key":"2024011920081329900_B49","doi-asserted-by":"crossref","first-page":"e0191553","DOI":"10.1371\/journal.pone.0191553","article-title":"Identification of microRNA that represses IRS-1 expression in liver","volume":"13","author":"Ono","year":"2018","journal-title":"PLoS One"},{"key":"2024011920081329900_B50","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.cell.2017.08.035","article-title":"Adipose tissue macrophage-derived exosomal miRNAs can modulate in\u00a0vivo and in\u00a0vitro insulin sensitivity","volume":"171","author":"Ying","year":"2017","journal-title":"Cell"},{"key":"2024011920081329900_B51","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/s41565-021-00931-2","article-title":"Extracellular vesicles as a next-generation drug delivery platform","volume":"16","author":"Herrmann","year":"2021","journal-title":"Nat Nanotechnol"},{"key":"2024011920081329900_B52","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1038\/s41586-022-04518-2","article-title":"A single-cell atlas of human and mouse white adipose tissue","volume":"603","author":"Emont","year":"2022","journal-title":"Nature"},{"key":"2024011920081329900_B53","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41574-021-00568-0","article-title":"The physiological role of \u03b2-cell heterogeneity in pancreatic islet function","volume":"18","author":"Benninger","year":"2022","journal-title":"Nat Rev Endocrinol"},{"key":"2024011920081329900_B54","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41556-023-01103-1","article-title":"A beta cell subset with enhanced insulin secretion and glucose metabolism is reduced in type 2 diabetes","volume":"25","author":"Rubio-Navarro","year":"2023","journal-title":"Nat Cell Biol"}],"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/73\/2\/169\/745703\/dbi230005.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/73\/2\/169\/745703\/dbi230005.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T15:08:30Z","timestamp":1705676910000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/73\/2\/169\/154096\/Adipose-Signals-Regulating-Distal-Organ-Health-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,19]]},"references-count":54,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,1,19]]},"published-print":{"date-parts":[[2024,2,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dbi23-0005","relation":{},"ISSN":["0012-1797"],"issn-type":[{"value":"0012-1797","type":"print"}],"subject":[],"published":{"date-parts":[[2024,1,19]]}}}