Brunetta 2018 Exp Physiol
|Brunetta HS, de Paula GC, de Oliveira J, Martins EL, Dos Santos GJ, Filho AG, Rafacho A, de Bem AF, Nunes EA (2018) Decrement in resting and insulin-stimulated soleus muscle mitochondrial respiration is an early event in diet-induced obesity in mice. Exp Physiol [Epub ahead of print].|
Abstract: Recently, significant attention has been given to the role of muscle mitochondrial function in the development of insulin resistance associated with obesity. Our aim was to investigate temporal alterations in mitochondrial respiration, H2O2 emission, and mitochondrial responsivity to insulin in permeabilized skeletal muscle-fibres during the development of obesity in mice. Swiss male mice (5-6 weeks old) were fed with a high-fat diet (60% calories from fat) or standard diet for 7, 14 and 28 days to induce obesity and insulin resistance. Diet-induced obese (DIO) mice presented reduced glucose tolerance and hyperinsulinemia after 7 days of HFD. After 14 days, the expected increase in muscle glycogen content after systemic injection of glucose and insulin was not observed in DIO mice. At 28 days, blood glucose decay after insulin injection was significantly impaired. Complex I (pyruvate + malate) and II (succinate) linked respiration, and oxidative phosphorylation (ADP) were decreased after 7 days of HFD and remained low in DIO mice after 14 and 28 days of treatment. Moreover, mitochondria from DIO mice were incapable of increasing respiratory coupling and ADP responsivity after insulin-stimulation in all observed periods. Mitochondrial content markers were reduced only after 28 days of treatment. Mitochondrial H2O2 emission profile varied during the time course of DIO, with a reduction of H2O2 emission in the early stages of DIO and an increased emission after 28 days of treatment. Our data demonstrate that DIO promotes transitory alterations in mitochondrial physiology during the early and late stages of insulin-resistance related to obesity.
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• Keywords: Diet-induced obesity, Insulin resistance, Mitochondrial function • Bioblast editor: Plangger M
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style Pathology: Obesity
Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Regulation: ADP Coupling state: LEAK, OXPHOS Pathway: N, NS, ROX HRR: Oxygraph-2k