{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T21:07:03Z","timestamp":1792876023954,"version":"4.5.0"},"reference-count":57,"publisher":"The Endocrine Society","issue":"4","license":[{"start":{"date-parts":[[2019,12,15]],"date-time":"2019-12-15T00:00:00Z","timestamp":1576368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Culture and Science of the State of North Rhine-Westphalia"},{"name":"German Federal Ministry of Health"},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["1116"],"award-info":[{"award-number":["1116"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"German Center for Diabetes Research"},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Context\/Objective<\/jats:title><jats:p>Impaired adipose tissue (AT) function might induce recent-onset type 2 diabetes (T2D). Understanding AT energy metabolism could yield novel targets for the treatment of T2D.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design\/Patients<\/jats:title><jats:p>Male patients with recently-diagnosed T2D and healthy male controls (CON) of similar abdominal subcutaneous AT (SAT)-thickness, fat mass, and age (n\u2005=\u200514 each), underwent hyperinsulinemic-euglycemic clamps with [6,6-2H2]glucose and indirect calorimetry. We assessed mitochondrial efficiency (coupling: state 3\/4o; proton leak: state 4o\/u) via high-resolution respirometry in superficial (SSAT) and deep (DSAT) SAT-biopsies, hepatocellular lipids (HCL) and fat mass by proton-magnetic-resonance-spectroscopy and -imaging.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>T2D patients (known diabetes duration: 2.5 [0.1; 5.0] years) had 43%, 44%, and 63% lower muscle insulin sensitivity (IS), metabolic flexibility (P\u2005&amp;lt;\u20050.01) and AT IS (P\u2005&amp;lt;\u20050.05), 73% and 31% higher HCL (P\u2005&amp;lt;\u20050.05), and DSAT-thickness (P\u2005&amp;lt;\u20050.001), but similar hepatic IS compared with CON. Mitochondrial efficiency was ~22% lower in SSAT and DSAT of T2D patients (P\u2005&amp;lt;\u20050.001) and ~8% lower in SSAT vs DSAT (P\u2005&amp;lt;\u20050.05). In both fat depots, mitochondrial coupling correlated positively with muscle IS and metabolic flexibility (r \u2265 0.40; P\u2005&amp;lt;\u20050.05), proton leak correlated positively (r \u2265 0.51; P\u2005&amp;lt;\u20050.01) and oxidative capacity negatively (r \u2264 \u22120.47; P\u2005&amp;lt;\u20050.05) with fasting free fatty acids (FFA). Metabolic flexibility correlated positively with SAT-oxidative capacity (r \u2265 0.48; P\u2005&amp;lt;\u20050.05) and negatively with DSAT-thickness (r = \u22120.48; P\u2005&amp;lt;\u20050.05). DSAT-thickness correlated negatively with mitochondrial coupling in both depots (r \u2264 \u22120.50; P\u2005&amp;lt;\u20050.01) and muscle IS (r = \u22120.59; P\u2005&amp;lt;\u20050.01), positively with FFA during clamp (r\u2005=\u20050.63; P\u2005&amp;lt;\u20050.001) and HCL (r\u2005=\u20050.49; P\u2005&amp;lt;\u20050.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Impaired mitochondrial function, insulin resistance, and DSAT expansion are AT abnormalities in recent-onset T2D that might promote whole-body insulin resistance and increased substrate flux to the liver.<\/jats:p><\/jats:sec>","DOI":"10.1210\/clinem\/dgz267","type":"journal-article","created":{"date-parts":[[2019,12,15]],"date-time":"2019-12-15T15:27:20Z","timestamp":1576423640000},"page":"e1331-e1343","source":"Crossref","is-referenced-by-count":24,"title":["Expansion and Impaired Mitochondrial Efficiency of Deep Subcutaneous Adipose Tissue in Recent-Onset Type 2 Diabetes"],"prefix":"10.1210","volume":"105","author":[{"given":"K\u00e1lm\u00e1n","family":"B\u00f3dis","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, D\u00fcsseldorf, Germany"},{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D\u00fcsseldorf, Germany"},{"name":"German Center for Diabetes Research (DZD), M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Jelenik","sequence":"first","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D\u00fcsseldorf, Germany"},{"name":"German Center for Diabetes Research (DZD), M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper","family":"Lundbom","sequence":"first","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D\u00fcsseldorf, Germany"},{"name":"German Center for Diabetes Research (DZD), M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel F","family":"Markgraf","sequence":"first","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D\u00fcsseldorf, Germany"},{"name":"German Center for Diabetes Research (DZD), M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Strom","sequence":"first","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D\u00fcsseldorf, Germany"},{"name":"German Center for Diabetes Research (DZD), M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana-Patricia","family":"Zaharia","sequence":"first","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D\u00fcsseldorf, Germany"},{"name":"German Center for Diabetes Research (DZD), M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanislava","family":"Karusheva","sequence":"first","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D\u00fcsseldorf, Germany"},{"name":"German Center for Diabetes Research (DZD), M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Burkart","sequence":"first","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D\u00fcsseldorf, Germany"},{"name":"German Center for Diabetes Research (DZD), M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"M\u00fcssig","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, D\u00fcsseldorf, Germany"},{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D\u00fcsseldorf, Germany"},{"name":"German Center for Diabetes Research (DZD), M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliya","family":"Kupriyanova","sequence":"first","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D\u00fcsseldorf, Germany"},{"name":"German Center for Diabetes Research (DZD), M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meriem","family":"Ouni","sequence":"first","affiliation":[{"name":"German Center for Diabetes Research (DZD), M\u00fcnchen-Neuherberg, Germany"},{"name":"Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbr\u00fccke, Nuthetal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Wolkersdorfer","sequence":"first","affiliation":[{"name":"Landesapotheke Salzburg, Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Hee","family":"Hwang","sequence":"first","affiliation":[{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D\u00fcsseldorf, Germany"},{"name":"German Center for Diabetes Research (DZD), M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Ziegler","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, D\u00fcsseldorf, Germany"},{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D\u00fcsseldorf, Germany"},{"name":"German Center for Diabetes Research (DZD), M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Sch\u00fcrmann","sequence":"first","affiliation":[{"name":"German Center for Diabetes Research (DZD), M\u00fcnchen-Neuherberg, Germany"},{"name":"Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbr\u00fccke, Nuthetal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Roden","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, D\u00fcsseldorf, Germany"},{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D\u00fcsseldorf, Germany"},{"name":"German Center for Diabetes Research (DZD), M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5185-8168","authenticated-orcid":false,"given":"Julia","family":"Szendroedi","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, D\u00fcsseldorf, Germany"},{"name":"Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, D\u00fcsseldorf, Germany"},{"name":"German Center for Diabetes Research (DZD), M\u00fcnchen-Neuherberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"GDS Study Group","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A E","family":"Buyken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Belgardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Geerling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Al-Hasani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Herder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J H","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Icks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Kotzka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O","family":"Kuss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Lammert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Markgraf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"M\u00fcssig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Rathmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Szendroedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Ziegler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Roden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2019,12,15]]},"reference":[{"issue":"4","key":"2020042119473228700_CIT0001","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1152\/physrev.00063.2017","article-title":"Mechanisms of insulin action and insulin resistance","volume":"98","author":"Petersen","year":"2018","journal-title":"Physiol Rev."},{"issue":"2","key":"2020042119473228700_CIT0002","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.mcna.2010.11.005","article-title":"Pathophysiology of prediabetes","volume":"95","author":"Ferrannini","year":"2011","journal-title":"Med Clin North Am."},{"issue":"2","key":"2020042119473228700_CIT0003","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s00125-018-4777-x","article-title":"The many secret lives of adipocytes: implications for diabetes","volume":"62","author":"Scherer","year":"2019","journal-title":"Diabetologia."},{"issue":"3","key":"2020042119473228700_CIT0004","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1152\/physrev.00015.2017","article-title":"Interorgan metabolic crosstalk in human insulin resistance","volume":"98","author":"Gancheva","year":"2018","journal-title":"Physiol Rev."},{"issue":"3","key":"2020042119473228700_CIT0005","doi-asserted-by":"crossref","first-page":"514","DOI":"10.2337\/dc08-1762","article-title":"Impact of different bariatric surgical procedures on insulin action and beta-cell function in type 2 diabetes","volume":"32","author":"Ferrannini","year":"2009","journal-title":"Diabetes Care."},{"issue":"9","key":"2020042119473228700_CIT0006","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/S2213-8587(19)30076-2","article-title":"Understanding the mechanisms of reversal of type 2 diabetes","volume":"7","author":"Taylor","year":"2019","journal-title":"Lancet Diabetes Endocrinol."},{"issue":"4","key":"2020042119473228700_CIT0007","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1053\/j.gastro.2012.02.003","article-title":"Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications","volume":"142","author":"Cusi","year":"2012","journal-title":"Gastroenterology."},{"issue":"2","key":"2020042119473228700_CIT0008","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.physbeh.2008.01.020","article-title":"Type 2 diabetes mellitus and skeletal muscle metabolic function","volume":"94","author":"Phielix","year":"2008","journal-title":"Physiol Behav."},{"issue":"7","key":"2020042119473228700_CIT0009","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1172\/JCI25758","article-title":"Skeletal muscle fat oxidation: timing and flexibility are everything","volume":"115","author":"Kelley","year":"2005","journal-title":"J Clin Invest."},{"issue":"3","key":"2020042119473228700_CIT0010","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1210\/er.2009-0027","article-title":"The role of mitochondria in the pathogenesis of type 2 diabetes","volume":"31","author":"Patti","year":"2010","journal-title":"Endocr Rev."},{"issue":"10","key":"2020042119473228700_CIT0011","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1007\/s00125-016-4038-9","article-title":"Metabolic flexibility and oxidative capacity independently associate with insulin sensitivity in individuals with newly diagnosed type 2 diabetes","volume":"59","author":"Apostolopoulou","year":"2016","journal-title":"Diabetologia."},{"issue":"45","key":"2020042119473228700_CIT0012","doi-asserted-by":"crossref","first-page":"30658","DOI":"10.1074\/jbc.M800510200","article-title":"Paradoxical effect of mitochondrial respiratory chain impairment on insulin signaling and glucose transport in adipose cells","volume":"283","author":"Shi","year":"2008","journal-title":"J Biol Chem."},{"issue":"4","key":"2020042119473228700_CIT0013","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1111\/febs.12096","article-title":"Mitochondrial dysfunction leads to impairment of insulin sensitivity and adiponectin secretion in adipocytes","volume":"280","author":"Wang","year":"2013","journal-title":"Febs J."},{"issue":"7","key":"2020042119473228700_CIT0014","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1002\/oby.21528","article-title":"Proteomics analyses of subcutaneous adipocytes reveal novel abnormalities in human insulin resistance","volume":"24","author":"Xie","year":"2016","journal-title":"Obesity (Silver Spring)."},{"issue":"10","key":"2020042119473228700_CIT0015","doi-asserted-by":"crossref","first-page":"4408","DOI":"10.1096\/fj.14-253971","article-title":"Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications","volume":"28","author":"Vernochet","year":"2014","journal-title":"Faseb J."},{"issue":"11","key":"2020042119473228700_CIT0016","doi-asserted-by":"crossref","first-page":"e13017","DOI":"10.1111\/eci.13017","article-title":"Energy metabolism of white adipose tissue and insulin resistance in humans","volume":"48","author":"B\u00f3dis","year":"2018","journal-title":"Eur J Clin Invest."},{"issue":"1","key":"2020042119473228700_CIT0017","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/2042-6410-3-13","article-title":"Sex differences in human adipose tissues - the biology of pear shape","volume":"3","author":"Karastergiou","year":"2012","journal-title":"Biol Sex Differ."},{"issue":"3","key":"2020042119473228700_CIT0018","doi-asserted-by":"crossref","first-page":"640","DOI":"10.2337\/dc11-1583","article-title":"Abdominal superficial subcutaneous fat: a putative distinct protective fat subdepot in type 2 diabetes","volume":"35","author":"Golan","year":"2012","journal-title":"Diabetes Care."},{"issue":"6","key":"2020042119473228700_CIT0019","doi-asserted-by":"crossref","first-page":"E1135","DOI":"10.1152\/ajpendo.0327.2001","article-title":"Abdominal fat distribution and peripheral and hepatic insulin resistance in type 2 diabetes mellitus","volume":"283","author":"Miyazaki","year":"2002","journal-title":"Am J Physiol Endocrinol Metab."},{"issue":"5","key":"2020042119473228700_CIT0020","doi-asserted-by":"crossref","first-page":"E941","DOI":"10.1152\/ajpendo.2000.278.5.E941","article-title":"Subdivisions of subcutaneous abdominal adipose tissue and insulin resistance","volume":"278","author":"Kelley","year":"2000","journal-title":"Am J Physiol Endocrinol Metab."},{"issue":"8","key":"2020042119473228700_CIT0021","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1038\/oby.2007.231","article-title":"Deep subcutaneous adipose tissue: a distinct abdominal adipose depot","volume":"15","author":"Walker","year":"2007","journal-title":"Obesity (Silver Spring)."},{"issue":"1","key":"2020042119473228700_CIT0022","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s12020-013-0040-x","article-title":"Obesity modifies expression profiles of metabolic markers in superficial and deep subcutaneous abdominal adipose tissue depots","volume":"46","author":"Walker","year":"2014","journal-title":"Endocrine."},{"issue":"4","key":"2020042119473228700_CIT0023","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1038\/ijo.2012.72","article-title":"Deep subcutaneous adipose tissue is more saturated than superficial subcutaneous adipose tissue","volume":"37","author":"Lundbom","year":"2013","journal-title":"Int J Obes (Lond)."},{"key":"2020042119473228700_CIT0024","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s12933-016-0374-9","article-title":"Cohort profile: the German Diabetes Study (GDS)","volume":"15","author":"Szendroedi","year":"2016","journal-title":"Cardiovasc Diabetol."},{"issue":"5","key":"2020042119473228700_CIT0025","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.2337\/diabetes.54.5.1392","article-title":"Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo","volume":"54","author":"Bogacka","year":"2005","journal-title":"Diabetes."},{"key":"2020042119473228700_CIT0026","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.2337\/dc19-S002","article-title":"2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2019","volume":"42","author":"American Diabetes Association","year":"2019","journal-title":"Diabetes care"},{"issue":"5","key":"2020042119473228700_CIT0027","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1111\/j.2047-6310.2013.00189.x","article-title":"Adipose tissue insulin resistance in adolescents with and without type 2 diabetes","volume":"9","author":"Kelsey","year":"2014","journal-title":"Pediatr Obes."},{"issue":"2","key":"2020042119473228700_CIT0028","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1079\/PNS2004349","article-title":"Metabolic flexibility","volume":"63","author":"Storlien","year":"2004","journal-title":"Proc Nutr Soc."},{"issue":"4","key":"2020042119473228700_CIT0029","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1210\/jc.2017-00047","article-title":"How to measure adipose tissue insulin sensitivity","volume":"102","author":"S\u00f8ndergaard","year":"2017","journal-title":"J Clin Endocrinol Metab."},{"issue":"10","key":"2020042119473228700_CIT0030","doi-asserted-by":"crossref","first-page":"3254","DOI":"10.2337\/dc12-2353","article-title":"Improved plasma FFA\/insulin homeostasis is independently associated with improved glucose tolerance after a 1-year lifestyle intervention in viscerally obese men","volume":"36","author":"Borel","year":"2013","journal-title":"Diabetes Care."},{"issue":"3","key":"2020042119473228700_CIT0031","doi-asserted-by":"crossref","first-page":"821","DOI":"10.2337\/dc13-1353","article-title":"Structural and functional properties of deep abdominal subcutaneous adipose tissue explain its association with insulin resistance and cardiovascular risk in men","volume":"37","author":"Marinou","year":"2014","journal-title":"Diabetes Care."},{"issue":"3","key":"2020042119473228700_CIT0032","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1007\/s00125-013-3127-2","article-title":"Reduction of non-esterified fatty acids improves insulin sensitivity and lowers oxidative stress, but fails to restore oxidative capacity in type 2 diabetes: a randomised clinical trial","volume":"57","author":"Phielix","year":"2014","journal-title":"Diabetologia."},{"issue":"1","key":"2020042119473228700_CIT0033","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1042\/BJ20080868","article-title":"High fat diet induces dysregulation of hepatic oxygen gradients and mitochondrial function in vivo","volume":"417","author":"Mantena","year":"2009","journal-title":"Biochem J."},{"issue":"6","key":"2020042119473228700_CIT0034","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1194\/jlr.M023382","article-title":"Elevated TCA cycle function in the pathology of diet-induced hepatic insulin resistance and fatty liver","volume":"53","author":"Satapati","year":"2012","journal-title":"J Lipid Res."},{"issue":"5","key":"2020042119473228700_CIT0035","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.cmet.2015.04.004","article-title":"Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis","volume":"21","author":"Koliaki","year":"2015","journal-title":"Cell Metab."},{"issue":"8","key":"2020042119473228700_CIT0036","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.2337\/db05-1574","article-title":"Free fatty acids inhibit insulin signaling-stimulated endothelial nitric oxide synthase activation through upregulating PTEN or inhibiting Akt kinase","volume":"55","author":"Wang","year":"2006","journal-title":"Diabetes."},{"issue":"6","key":"2020042119473228700_CIT0037","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.2337\/diabetes.54.6.1640","article-title":"Dose-response effect of elevated plasma free fatty acid on insulin signaling","volume":"54","author":"Belfort","year":"2005","journal-title":"Diabetes."},{"issue":"1","key":"2020042119473228700_CIT0038","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1210\/en.2006-1132","article-title":"Vascular lipotoxicity: endothelial dysfunction via fatty-acid-induced reactive oxygen species overproduction in obese Zucker diabetic fatty rats","volume":"148","author":"Chinen","year":"2007","journal-title":"Endocrinology."},{"issue":"11","key":"2020042119473228700_CIT0039","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.2337\/diabetes.49.11.1939","article-title":"High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C\u2013dependent activation of NAD(P)H oxidase in cultured vascular cells","volume":"49","author":"Inoguchi","year":"2000","journal-title":"Diabetes."},{"issue":"7","key":"2020042119473228700_CIT0040","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1007\/s00125-010-1684-1","article-title":"Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009","volume":"53","author":"DeFronzo","year":"2010","journal-title":"Diabetologia"},{"issue":"4","key":"2020042119473228700_CIT0041","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.cld.2009.07.009","article-title":"Role of insulin resistance and lipotoxicity in non-alcoholic steatohepatitis","volume":"13","author":"Cusi","year":"2009","journal-title":"Clin Liver Dis."},{"issue":"2","key":"2020042119473228700_CIT0042","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nrendo.2011.138","article-title":"The role of mitochondria in insulin resistance and type 2 diabetes mellitus","volume":"8","author":"Szendroedi","year":"2011","journal-title":"Nat Rev Endocrinol."},{"key":"2020042119473228700_CIT0043","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1146\/annurev-nutr-071715-050656","article-title":"Alterations of mitochondrial function and insulin sensitivity in human obesity and diabetes mellitus","volume":"36","author":"Koliaki","year":"2016","journal-title":"Annu Rev Nutr."},{"key":"2020042119473228700_CIT0044","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.molmet.2018.01.017","article-title":"Small molecule PGC-1\u03b11 protein stabilizers induce adipocyte Ucp1 expression and uncoupled mitochondrial respiration","volume":"9","author":"Pettersson-Klein","year":"2018","journal-title":"Mol Metab."},{"key":"2020042119473228700_CIT0045","article-title":"Role of adipocyte mitochondria in inflammation, lipemia and insulin sensitivity in humans: effects of pioglitazone treatment","author":"Xie","year":"2017","journal-title":"(2005)"},{"issue":"12","key":"2020042119473228700_CIT0046","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1016\/j.metabol.2011.04.015","article-title":"Mitochondrial bioenergetics is not impaired in nonobese subjects with type 2 diabetes mellitus","volume":"60","author":"Chattopadhyay","year":"2011","journal-title":"Metabolism."},{"issue":"10","key":"2020042119473228700_CIT0047","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1002\/oby.21223","article-title":"Adipose tissue mitochondrial respiration and lipolysis before and after a weight loss by diet and RYGB","volume":"23","author":"Hansen","year":"2015","journal-title":"Obesity (Silver Spring)."},{"issue":"14","key":"2020042119473228700_CIT0048","doi-asserted-by":"crossref","first-page":"8466","DOI":"10.1073\/pnas.1032913100","article-title":"Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1","volume":"100","author":"Patti","year":"2003","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"4","key":"2020042119473228700_CIT0049","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1002\/bms.1200070407","article-title":"Measurement of plasma free fatty acid turnover and oxidation using [1-13C]palmitic acid","volume":"7","author":"Wolfe","year":"1980","journal-title":"Biomed Mass Spectrom."},{"issue":"2","key":"2020042119473228700_CIT0050","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0014-5793(81)81168-4","article-title":"Decreased insulin sensitivity due to a postreceptor defect as a consequence of ATP-deficiency in fat cells","volume":"132","author":"H\u00e4ring","year":"1981","journal-title":"FEBS Lett."},{"key":"2020042119473228700_CIT0051","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13098-016-0127-7","article-title":"Relationship between deep subcutaneous abdominal adipose tissue and metabolic syndrome: a case control study","volume":"8","author":"Kim","year":"2016","journal-title":"Diabetol Metab Syndr."},{"issue":"10","key":"2020042119473228700_CIT0052","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1001\/archinte.167.10.1068","article-title":"Prediction of incident diabetes mellitus in middle-aged adults: the Framingham Offspring Study","volume":"167","author":"Wilson","year":"2007","journal-title":"Arch Intern Med."},{"issue":"10","key":"2020042119473228700_CIT0053","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1007\/s00125-013-3002-1","article-title":"Family history of diabetes is associated with higher risk for prediabetes: a multicentre analysis from the German Center for Diabetes Research","volume":"56","author":"Wagner","year":"2013","journal-title":"Diabetologia."},{"issue":"8","key":"2020042119473228700_CIT0054","doi-asserted-by":"crossref","first-page":"e105262","DOI":"10.1371\/journal.pone.0105262","article-title":"Adipocyte hypertrophy, inflammation and fibrosis characterize subcutaneous adipose tissue of healthy, non-obese subjects predisposed to type 2 diabetes","volume":"9","author":"Henninger","year":"2014","journal-title":"Plos One."},{"key":"2020042119473228700_CIT0055","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ejim.2015.11.027","article-title":"Predictors of abdominal adipose tissue compartments: 18-year follow-up of young men with and without family history of diabetes","volume":"29","author":"Sk\u00e5rn","year":"2016","journal-title":"Eur J Intern Med."},{"issue":"9467","key":"2020042119473228700_CIT0056","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1016\/S0140-6736(05)61032-X","article-title":"Type 2 diabetes: principles of pathogenesis and therapy","volume":"365","author":"Stumvoll","year":"2005","journal-title":"Lancet."},{"issue":"5","key":"2020042119473228700_CIT0057","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1002\/oby.22435","article-title":"Adipose mitochondrial respiratory capacity in obesity is impaired independently of glycemic status of tissue donors","volume":"27","author":"Wessels","year":"2019","journal-title":"Obesity (Silver Spring)."}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgz267\/31532226\/dgz267.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/105\/4\/e1331\/33110250\/dgz267.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/105\/4\/e1331\/33110250\/dgz267.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T01:15:19Z","timestamp":1695518119000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/105\/4\/e1331\/5678088"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,15]]},"references-count":57,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,4,1]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgz267","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,4]]},"published":{"date-parts":[[2019,12,15]]}}}