Mitochondrial antioxidative capacity regulates muscle glucose uptake in the conscious mouse: effect of exercise and diet.

Kang L, Lustig ME, Bonner JS, Lee-Young RS, Mayes WH, James FD, Lin CT, Perry CG, Anderson EJ, Neufer PD, Wasserman DH
J Appl Physiol (1985). 2012 113 (8): 1173-83

PMID: 22653994 · PMCID: PMC3472490 · DOI:10.1152/japplphysiol.01344.2011

The objective of this study was to test the hypothesis that exercise-stimulated muscle glucose uptake (MGU) is augmented by increasing mitochondrial reactive oxygen species (mtROS) scavenging capacity. This hypothesis was tested in genetically altered mice fed chow or a high-fat (HF) diet that accelerates mtROS formation. Mice overexpressing SOD2 (sod2(Tg)), mitochondria-targeted catalase (mcat(Tg)), and combined SOD2 and mCAT (mtAO) were used to increase mtROS scavenging. mtROS was assessed by the H(2)O(2) emitting potential (JH(2)O(2)) in muscle fibers. sod2(Tg) did not decrease JH(2)O(2) in chow-fed mice, but decreased JH(2)O(2) in HF-fed mice. mcat(Tg) and mtAO decreased JH(2)O(2) in both chow- and HF-fed mice. In parallel, the ratio of reduced to oxidized glutathione (GSH/GSSG) was unaltered in sod2(Tg) in chow-fed mice, but was increased in HF-fed sod2(Tg) and both chow- and HF-fed mcat(Tg) and mtAO. Nitrotyrosine, a marker of NO-dependent, reactive nitrogen species (RNS)-induced nitrative stress, was decreased in both chow- and HF-fed sod2(Tg), mcat(Tg), and mtAO mice. This effect was not changed with exercise. Kg, an index of MGU was assessed using 2-[(14)C]-deoxyglucose during exercise. In chow-fed mice, sod2(Tg), mcat(Tg), and mtAO increased exercise Kg compared with wild types. Exercise Kg was also augmented in HF-fed sod2(Tg) and mcat(Tg) mice but unchanged in HF-fed mtAO mice. In conclusion, mtROS scavenging is a key regulator of exercise-mediated MGU and this regulation depends on nutritional state.

MeSH Terms (21)

Action Potentials Animal Feed Animals Antioxidants Biological Transport Catalase Diet, High-Fat Glucose Glutathione Disulfide Hydrogen Peroxide Mice Mice, Inbred C57BL Mice, Transgenic Mitochondria Muscle, Skeletal Nitric Oxide Physical Conditioning, Animal Reactive Nitrogen Species Reactive Oxygen Species Superoxide Dismutase Tyrosine

Connections (5)

This publication is referenced by other Labnodes entities: