title: Tissue-specific control of mitochondrial respiration in obesity-related insulin resistance and diabetes.
abstract: The tissue-specific role of mitochondrial respiratory capacity in the development of insulin resistance and type 2 diabetes is unclear. We determined mitochondrial function in glycolytic and oxidative skeletal muscle and liver from lean (+/?) and obese diabetic (db/db) mice. In lean mice, the mitochondrial respiration pattern differed between tissues. Tissue-specific mitochondrial profiles were then compared between lean and db/db mice. In liver, mitochondrial respiratory capacity and protein expression, including peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), was decreased in db/db mice, consistent with increased mitochondrial fission. In glycolytic muscle, mitochondrial respiration, as well as protein and mRNA expression of mitochondrial markers, was increased in db/db mice, suggesting increased mitochondrial content and fatty acid oxidation capacity. In oxidative muscle, mitochondrial complex I function and PGC-1α and mitochondrial transcription factor A (TFAM) protein levels were decreased in db/db mice, along with increased level of proteins related to mitochondrial dynamics. In conclusion, mitochondrial respiratory performance is under the control of tissue-specific mechanisms and is not uniformly altered in response to obesity. Furthermore, insulin resistance in glycolytic skeletal muscle can be maintained by a mechanism independent of mitochondrial dysfunction. Conversely, insulin resistance in liver and oxidative skeletal muscle from db/db mice is coincident with mitochondrial dysfunction.
authors.affiliation: Karolinska Institutet, Section of Integrative Physiology, Stockholm, Sweden.
authors.forename: Maria H
authors.initials: MH
authors.lastname: Holmström
authors.forename: Eduardo
authors.initials: E
authors.lastname: Iglesias-Gutierrez
authors.forename: Juleen R
authors.initials: JR
authors.lastname: Zierath
authors.forename: Pablo M
authors.initials: PM
authors.lastname: Garcia-Roves
mesh_terms: D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D006003:Glycogen / Q000097:blood; D006019:Glycolysis; D006609:High Mobility Group Proteins / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008820:Mice, Obese; D008928:Mitochondria / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D060888:Real-Time Polymerase Chain Reaction; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C081930:Tfam protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D014280:Triglycerides; D006003:Glycogen