The purpose of this study was to compare oxidative modification of blood proteins, lipids, DNA, and glutathione in the 24 hours following aerobic and anaerobic exercise using similar muscle groups. Ten cross-trained men (24.3 +/- 3.8 years, [mean +/- SEM]) performed in random order 30 minutes of continuous cycling at 70% of Vo(2)max and intermittent dumbbell squatting at 70% of 1 repetition maximum (1RM), separated by 1-2 weeks, in a crossover design. Blood samples taken before, and immediately, 1, 6, and 24 hours postexercise were analyzed for plasma protein carbonyls (PC), plasma malondialdehyde (MDA), and whole-blood total (TGSH), oxidized (GSSG), and reduced (GSH) glutathione. Blood samples taken before and 24 hours postexercise were analyzed for serum 8-hydroxy-2'-deoxyguanosine (8-OHdG). PC values were greater at 6 and 24 hours postexercise compared with pre-exercise for squatting, with greater PC values at 24 hours postexercise for squatting compared with cycling (0.634 +/- 0.053 vs. 0.359 +/- 0.018 nM.mg protein(-1)). There was no significant interaction or main effects for MDA or 8-OHdG. GSSG experienced a short-lived increase and GSH a transient decrease immediately following both exercise modes. These data suggest that 30 minutes of aerobic and anaerobic exercise performed by young, cross-trained men (a) can increase certain biomarkers of oxidative stress in blood, (b) differentially affect oxidative stress biomarkers, and (c) result in a different magnitude of oxidation based on the macromolecule studied. Practical applications: While protein and glutathione oxidation was increased following acute exercise as performed in this study, future research may investigate methods of reducing macromolecule oxidation, possibly through the use of antioxidant therapy.

SummaryWith the increasing prevalence of obesity, research has focused on the molecular mechanism(s) linking obesity and skeletal muscle insulin resistance. Metabolic alterations within muscle, such as changes in the cellular location of fatty acid transporter proteins, decreased mitochondrial enzyme activity, and defects in mitochondrial morphology, likely contribute to obesity and insulin resistance. These defects are thought to play a role in the reduced skeletal muscle fatty acid oxidation and increased intramuscular lipid (IMCL) accumulation that is apparent with obesity and other insulin-resistant states such as type 2 diabetes. Intramuscular triacylglycerol does not appear to be a ubiquitous marker of insulin resistance, although specific IMCL intermediates such as long-chain fatty acyl-CoAs, ceramide, and diacylglycerol may inhibit insulin signal transduction. In this review, we will briefly summarize the defects in skeletal muscle lipid metabolism associated with obesity, and discuss the proposed mechanisms by which these defects may contribute to insulin resistance. IUBMBIUBMB Life, 61(1): [47][48][49][50][51][52][53][54][55] 2009

Cultured myocytes from severely obese women express perturbations in FA metabolism and insulin signaling reminiscent of those observed in vivo. The obesity phenotype can be recapitulated in muscle cells from lean subjects via exposure to excess lipid, but not by overexpressing the FAT/CD36 FA transporter.

Abstract:The purpose of this study was to determine the effect of aerobic exercise duration on plasma protein carbonyl concentrations, a marker of protein oxidation, in aerobically trained men and women. Eight men (age: 27 ± 4 years, V·O 2peak : 4.09 ± 0.26 L · min -1 ; mean ± SD) and 7 women (age: 27 ± 6 years, V·O 2peak : 2.33 ± 0.24 L · min -1 ) exercised on an electrically-braked cycle ergometer at 70 % V·O 2peak for 30, 60 or 120 minutes on three separate days. Plasma samples collected before and immediately, 30-and 60-minutes post-exercise were analyzed for protein carbonyls. Mean oxygen uptake was greater for men in all conditions (2.75 ± 0.03 L · min -1 ; 38 ± 0.43 ml · kg -1 · min -1 ) compared to women (1.57 ± 0.03 L · min -1 ; 24.1 ± 0.47 ml · kg -1 · min -1 ). Total work performed during the exercise sessions was also greater for men than for women during the 30 (368 ± 11 versus 223 ± 7 kJ), 60 (697 ± 17 versus 423 ± 18 kJ), and 120-minute conditions (1173 ± 44 versus 726 ± 28 kJ) (Mean ± SEM). Although these comparisons were significant (p < 0.0001), sex differences in total work performed and mean V·O 2 did not result in sex differences in protein carbonyls. However, a condition by time interaction was observed with greater post-exercise values following the 120-minute condition compared to both the 30-and 60-minute conditions. Protein carbonyl concentration was greatest immediately post-exercise for both men and women and generally declined in a linear trend through one hour of recovery. These data suggest that protein carbonyl concentration is elevated by cycling exercise performed at 70 % V·O 2peak , is greater following longer duration rides, begins to recover within one hour following exercise, and is not different between men and women.

The purpose of this study was to determine if site-specific phosphorylation at the level of Akt substrate of 160 kDa (AS160) is altered in skeletal muscle from sedentary humans across a wide range of the adult life span (18–84 years of age) and if endurance- and/or strength-oriented exercise training could rescue decrements in insulin action and skeletal muscle AS160 phosphorylation. A euglycemic-hyperinsulinemic clamp and skeletal muscle biopsies were performed in 73 individuals encompassing a wide age range (18–84 years of age), and insulin-stimulated AS160 phosphorylation was determined. Decrements in whole-body insulin action were associated with impairments in insulin-induced phosphorylation of skeletal muscle AS160 on sites Ser-588, Thr-642, Ser-666, and phospho-Akt substrate, but not Ser-318 or Ser-751. Twelve weeks of endurance- or strength-oriented exercise training increased whole-body insulin action and reversed impairments in AS160 phosphorylation evident in insulin-resistant aged individuals. These findings suggest that a dampening of insulin-induced phosphorylation of AS160 on specific sites in skeletal muscle contributes to the insulin resistance evident in a sedentary aging population and that exercise training is an effective intervention for treating these impairments.

Thirty cross-trained, female subjects (19-69 years) completed an endurance exercise session (ES), a resistance exercise session (RS), and a control session (CS) in a randomized, balanced design. The ES consisted of 40 minutes of cycling at 75% maximum heart rate, and the RS consisted of 3 sets of 10 repetitions of eight exercises. During the CS, subjects performed no exercise. Before and after exercise, and after 30 minutes of recovery, blood samples were analyzed for plasma lactate and serum growth hormone, insulin-like growth factor 1, testosterone, estradiol, dehydroepiandrosterone, and cortisol. Samples were taken during the CS at the same intervals as during the exercise sessions. There were no age-related differences in intensity measures during exercise. Absolute change from baseline in testosterone (p <.001), estradiol (p <.05), and growth hormone (p <.01) was significantly greater in the ES and RS compared with that in the CS. Absolute change in dehydroepiandrosterone was significantly greater in the RS only (p <.05). Results indicate that an acute bout of exercise can increase concentrations of anabolic hormones in females across a wide age range.

OBJECTIVETo determine whether the obesity-related decrement in fatty acid oxidation (FAO) in primary human skeletal muscle cells (HSkMC) is linked with lower mitochondrial content and whether this deficit could be corrected via overexpression of peroxisome proliferator–activated receptor-γ coactivator-1α (PGC-1α).RESEARCH DESIGN AND METHODSFAO was studied in HSkMC from lean (BMI 22.4 ± 0.9 kg/m2; N = 12) and extremely obese (45.3 ± 1.4 kg/m2; N = 9) subjects. Recombinant adenovirus was used to increase HSkMC PGC-1α expression (3.5- and 8.0-fold), followed by assessment of mitochondrial content (mtDNA and cytochrome C oxidase IV [COXIV]), complete (14CO2 production from labeled oleate), and incomplete (acid soluble metabolites [ASM]) FAO, and glycerolipid synthesis.RESULTSObesity was associated with a 30% decrease (P < 0.05) in complete FAO, which was accompanied by higher relative rates of incomplete FAO ([14C]ASM production/14CO2), increased partitioning of fatty acid toward storage, and lower (P < 0.05) mtDNA (−27%), COXIV (−35%), and mitochondrial transcription factor (mtTFA) (−43%) protein levels. PGC-1α overexpression increased (P < 0.05) FAO, mtDNA, COXIV, mtTFA, and fatty acid incorporation into triacylglycerol in both lean and obese groups. Perturbations in FAO, triacylglycerol synthesis, mtDNA, COXIV, and mtTFA in obese compared with lean HSkMC persisted despite PGC-1α overexpression. When adjusted for mtDNA and COXIV content, FAO was equivalent between lean and obese groups.CONCLUSIONReduced mitochondrial content is related to impaired FAO in HSkMC derived from obese individuals. Increasing PGC-1α protein levels did not correct the obesity-related absolute reduction in FAO or mtDNA content, implicating mechanisms other than PGC-1α abundance.

These findings indicate a differential response to a lipid stimulus in the skeletal muscle of lean and insulin resistant obese humans.