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 [Epub ahead of print].

» PMID: 25845660

Ludzki A, Paglialunga S, Smith BK, Herbst EA, Allison MK, Heigenhauser GJ, Neufer PD, Holloway GP (2015) Diabetes

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

• O2k-Network Lab: CA Guelph Holloway GP, NL Maastricht Schrauwen P, US NC Greenville Neufer PD, CA Guelph Holloway GP

Labels: MiParea: Exercise physiology;nutrition;life style  Pathology: Diabetes 

Organism: Human, Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 

Regulation: Fatty acid  Coupling state: LEAK, OXPHOS 

HRR: Oxygraph-2k 

Labels, [Epub ahead of print]