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High fat diet markedly elevates mitochondrial oxidant producing potential in skeletal muscle
Author(s) -
Anderson Ethan J.,
Neufer P. Darrell
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a817-b
Subject(s) - skeletal muscle , endocrinology , medicine , rotenone , antimycin a , mitochondrion , mitochondrial ros , chemistry , superoxide , biochemistry , biology , enzyme
Obesity/Type II Diabetes are associated with a profound loss of mitochondrial content and function in skeletal muscle. To investigate whether a high fat diet (HFD) affects the sensitivity and/or responsiveness of mitochondria to redox conditions favoring superoxide production (oxidant producing potential; OPP) in muscle, male Sprague‐Dawley rats were fed lard (100% fat) for 3 days (HF3D) or high‐fat chow (65% fat) for 3 weeks (HF3W) and mitochondrial H 2 O 2 production ( J H 2 O 2 ) was measured in permeabilized red (RG) and white (WG) gastrocnemius muscle fiber bundles in response to titration of: 1) complex II succinate (induces ΔΨ‐dependent superoxide production at complex I), 2) complex I pyruvate/malate (P/M) in the presence of rotenone (complex I inhibitor), and 3) P/M in the presence of antimycin A (complex III inhibitor). Surprisingly, in RG, J H 2 O 2 V max increased by 3.5 and 2‐fold (P<0.01) during titrations with succinate in HF3D and HF3W, respectively, compared with chow‐fed controls. Also in RG, J H 2 O 2 V max increased by 2‐fold (P<0.02) during titrations with P/M in the presence of antimycin A, and 1.7‐fold (P<0.05) in the presence of rotenone in HF3D versus chow‐fed controls. No significant differences in K m were observed in RG, nor were any differences observed in J H 2 O 2 V max or K m in WG for any conditions. These data demonstrate that a HFD dramatically increases mitochondrial OPP in red skeletal muscle, representing a potential causative factor in the loss of mitochondrial content and function associated with obesity and Type II Diabetes.