title: Alterations of Mitochondrial Function and Insulin Sensitivity in Human Obesity and Diabetes Mellitus.
abstract: Mitochondrial function refers to a broad spectrum of features such as resting mitochondrial activity, (sub)maximal oxidative phosphorylation capacity (OXPHOS), and mitochondrial dynamics, turnover, and plasticity. The interaction between mitochondria and insulin sensitivity is bidirectional and varies depending on tissue, experimental model, methodological approach, and features of mitochondrial function tested. In human skeletal muscle, mitochondrial abnormalities may be inherited (e.g., lower mitochondrial content) or acquired (e.g., impaired OXPHOS capacity and plasticity). Abnormalities ultimately lead to lower mitochondrial functionality due to or resulting in insulin resistance and type 2 diabetes mellitus. Similar mechanisms can also operate in adipose tissue and heart muscle. In contrast, mitochondrial oxidative capacity is transiently upregulated in the liver of obese insulin-resistant humans with or without fatty liver, giving rise to oxidative stress and declines in advanced fatty liver disease. These data suggest a highly tissue-specific interaction between insulin sensitivity and oxidative metabolism during the course of metabolic diseases in humans.
authors.affiliation: Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf 40225, Germany.|Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf 40225, Germany.|German Center for Diabetes Research (DZD e.V.), Düsseldorf 40225, Germany; email: Michael.Roden@ddz.uni-duesseldorf.de.
authors.forename: Chrysi
authors.initials: C
authors.lastname: Koliaki
authors.affiliation: Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf 40225, Germany.|Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf 40225, Germany.|German Center for Diabetes Research (DZD e.V.), Düsseldorf 40225, Germany; email: Michael.Roden@ddz.uni-duesseldorf.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D019317:Evidence-Based Medicine; D006801:Humans; D007333:Insulin Resistance; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism; D063269:Mitochondrial Turnover; D008954:Models, Biological; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology; D009765:Obesity / Q000378:metabolism* / Q000503:physiopathology; D009928:Organ Specificity; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress
keywords: bioenergetic adaptation; insulin resistance; mitochondrial dynamics; mitochondrial function; oxidative phosphorylation; tissue-specificity