Ludzki 2015 Diabetes
|Ludzki A, Paglialunga S, Smith BK, Herbst EA, Allison MK, Heigenhauser GJ, Neufer PD, Holloway GP (2015) Rapid repression of ADP transport by palmitoyl-CoA is attenuated by exercise training in humans; a potential mechanism to decrease oxidative stress and improve skeletal muscle insulin signaling. Diabetes 64:2769-79.|
Abstract: Mitochondrial ADP transport may represent a convergence point unifying two prominent working models for the development of insulin resistance, as reactive lipids (specifically palmitoyl-CoA [P-CoA]) can inhibit ADP transport and subsequently increase mitochondrial reactive oxygen species emissions. In the current study we aimed to determine if exercise training in humans diminished P-CoA attenuation of mitochondrial ADP respiratory sensitivity. Six weeks of exercise training increased whole-body glucose homeostasis and skeletal muscle Akt signaling and reduced markers of oxidative stress without reducing maximal mitochondrial H2O2 emissions. To ascertain if enhanced mitochondrial ADP transport contributed to the improvement in the in vivo oxidative state, we determined mitochondrial ADP sensitivity in the presence and absence of P-CoA. In the absence of P-CoA, exercise training reduced mitochondrial ADP sensitivity. In contrast, exercise training increased mitochondrial ADP sensitivity with P-CoA present. We further show that P-CoA noncompetitively inhibits mitochondrial ADP transport and the ability of ADP to attenuate mitochondrial H2O2 emission. Altogether, the current data provide a potential mechanism for how P-CoA contributes to insulin resistance and highlight the ability of exercise training to diminish P-CoA attenuation in mitochondrial ADP transport.
• Keywords: Mitochondria, Long chain fatty acyl-CoA, ADP transport, Type II diabetes, Skeletal muscle, Reactive oxygen species, Amplex Red, Blebbistatin, Buffer z
Labels: MiParea: Respiration, Exercise physiology;nutrition;life style Pathology: Diabetes
Organism: Human, Mouse Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue Enzyme: Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase Regulation: ADP, Fatty acid Coupling state: LEAK, OXPHOS Pathway: F, N, NS HRR: Oxygraph-2k