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Excess dietary fat depletes glutathione, increases mitochondrial oxidant emitting potential and shifts redox balance to a more oxidized state in human skeletal muscle
Author(s) -
Anderson Ethan J.,
Boyle Kristen E.,
Houmard Joseph A.,
Neufer P. Darrell
Publication year - 2008
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.22.1_supplement.958.6
Subject(s) - glutathione , chemistry , skeletal muscle , medicine , endocrinology , respiration , carnitine , meal , redox , antioxidant , oxidative phosphorylation , biochemistry , biology , food science , anatomy , enzyme , organic chemistry
The worldwide epidemic of Type 2 Diabetes is linked to modern lifestyle, of which high dietary fat intake is a substantial component. To examine the molecular impact of a high fat diet on human skeletal muscle mitochondria, male (18–34 yrs) subjects were recruited and muscle biopsies were obtained following a 12‐hour fast (A), 4 hours after a single high‐fat meal (65–70% fat content, B), and after 5 days of high‐fat diet/12‐hour fast (C). Using a method to measure in situ mitochondrial respiration and H 2 O 2 emission (mH 2 O 2 , an index of reactive oxygen species) in permeabilized muscle fibers supported by glutamate/malate (G/M), succinate (S), and palmitoyl‐carnitine (PC), we observed from A to both B and C a striking 2.5‐ and 3‐fold (P<0.05) increase in V max of G/M/S and PC‐supported mH 2 O 2 emission, respectively. Surprisingly, from A to C the total glutathione content (GSH t ) was decreased by 40% (P<0.05), and the GSH/GSSG ratio decreased by 2.5‐fold (P<0.05). Respiration with all substrates remained unchanged from A to B, but basal and maximal G/M/S‐supported respiration was decreased by 30% (P<0.05) at C. These data demonstrate that an excess dietary fat intake 1) increases skeletal muscle mH 2 O 2 emission and shifts redox balance to a more oxidized state, 2) decreases capacity for scavenging mH 2 O 2 by depleting GSH t , 3) decreases mitochondrial respiration, all potentially contributing to the etiology of Type 2 diabetes.