Physiological and biochemical correlates of increased work in trained iron-deficient rats

We investigated physiological and biochemical factors associated with the improved work capacity of trained iron-deficient rats. Female 21-day-old rats were assigned to one of four groups, two dietary groups (50 and 6 ppm dietary iron) subdivided into two levels of activity (sedentary and treadmill trained). Iron deficiency decreased hemoglobin (61%), maximal O2 uptake. (VO2max) (40%), skeletal muscle mitochondrial oxidase activities (59-90%), and running endurance (94%). In contrast, activities of tricarboxylic acid (TCA) cycle enzymes in skeletal muscle were largely unaffected. Four weeks of mild training in iron-deficient rats resulted in improved blood lactate homeostasis during exercise and increased VO2max (15%), TCA cycle enzymes of skeletal muscle (27-58%) and heart (29%), and liver NADH oxidase (34%) but did not affect any of these parameters in the iron-sufficient animals. In iron-deficient rats training affected neither the blood hemoglobin level nor any measured iron-dependent enzyme pathway of skeletal muscle but substantially increased endurance (230%). We conclude that the training-induced increase in endurance in iron-deficient rats may be related to cardiovascular improvements, elevations in liver oxidative capacity, and increases in the activities of oxidative enzymes that do not contain iron in skeletal and cardiac muscle.     

2-D DIGE analysis of the mitochondrial proteome from human skeletal muscle reveals time course-dependent remodelling in response to 14 consecutive days of endurance exercise training

Adaptation of skeletal muscle to repeated bouts of endurance exercise increases aerobic capacity and improves mitochondrial function. However, the adaptation of human skeletal muscle mitochondrial proteome to short‐term endurance exercise training has not been investigated. Eight sedentary males cycled for 60 min at 80% of peak oxygen consumption (VO_2peak) each day for 14 consecutive days, resulting in an increase in VO_2peak of 17.5±3.8% (p<0.01). Mitochondria‐enriched protein fractions from skeletal muscle biopsies taken from m. vastus lateralis at baseline, and on the morning following the 7th and 14th training sessions were subjected to 2‐D DIGE analysis with subsequent MS followed by database interrogation to identify the proteins of interest. Thirty‐one protein spots were differentially expressed after either 7 or 14 days of training (ANOVA, p<0.05). These proteins included subunits of the electron transport chain, enzymes of the tricarboxylic acid cycle, phosphotransfer enzymes, and regulatory factors in mitochondrial protein synthesis, oxygen transport, and antioxidant capacity. Several proteins demonstrated a time course‐dependent induction during training. Our results illustrate the phenomenon of skeletal muscle plasticity with the extensive remodelling of the mitochondrial proteome occurring after just 7 days of exercise training suggestive of enhanced capacity for adenosine triphosphate generation at a cellular level.     

Hepatic adaptations to iron deficiency and exercise training.

Brooks et al. [Am. J. Physiol. 253 (Endocrinol. Metab. 16): E461-E466, 1987] demonstrated an elevated gluconeogenic rate in resting iron-deficient rats. Because physical exercise also imposes demand on this hepatic function, we hypothesized that exercise training superimposed on iron deficiency would augment the hepatic capacity for amino acid transamination/deamination and pyruvate carboxylation. Sprague-Dawley rats (n = 32) were obtained at weaning (21 days of age) and randomly assigned to iron-sufficient (dietary iron = 60 mg iron/kg diet) or iron-deficient (3 mg iron/kg) dietary groups. Dietary groups were subdivided into sedentary and trained subgroups. Treadmill training was 4 wk in duration, 6 days/wk, 1 h/day, 0% grade. Treadmill speed was initially 26.8 m/min and was decreased to 14.3 m/min over the 4-wk training period. The mild exercise-training regimen did not affect any measured variable in iron-sufficient rats. In contrast, in iron-deficient animals, training increased endurance capacity threefold and reduced blood lactate and the lactate-to-alanine ratio during submaximal exercise by 34 and 27%, respectively. The mitochondrial oxidative capacity of gastrocnemius muscle was increased 46% by training. However, the oxidative capacity of liver was not affected by either iron deficiency or training. Maximal rates of pyruvate carboxylation and glutamine metabolism by isolated liver mitochondria were also evaluated. Iron deficiency and training interacted to increase pyruvate carboxylation by intact mitochondria. Glutamine metabolism was increased roughly threefold by iron deficiency alone, and training amplified this effect to a ninefold increase over iron-sufficient animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Muscle mitochondrial ultrastructure in exercise-trained iron-deficient rats

To investigate effects of endurance training and iron deficiency, as well as the combination of these two conditions, on mitochondrial ultrastructure, weanling rats at 3 wk of age were assigned to iron-deficient (Fe-) and iron-sufficient (Fe+) groups. Subsequently, groups were subdivided into exercise-trained (T) and sedentary (S) groups. Electron microscopy showed subsarcolemmal and intrafibrillar mitochondria in the Fe-T animals to be enlarged with sparse cristae and vacuole-like areas compared with the other groups. An increase in the number of lipid droplets in both Fe- groups was observed. Stereological measurements revealed a 99% increase in the volume occupied by muscle mitochondria in the Fe-T animals (11.9 +/- 0.8%) over the Fe+T (5.9 +/- 0.4%) and Fe+S (6.0 +/- 0.3%) groups and a 55% increase over the Fe-S groups (7.7 +/- 0.3%). The ratio of mitochondrial surface area to tissue volume was significantly decreased only in the Fe-T group. These results indicate that the combined stresses of iron deficiency and training produce mitochondrial ultrastructural changes far greater than those of iron deficiency or training alone. Because this is also the case with the disproportion among mitochondrial enzymes, it is possible that the ultrastructural changes are indicative of morphological responses that maintain ATP turnover during exercise in iron deficiency when oxygen transport and electron transport chain activities are reduced.     

Bitter melon seed oil increases mitochondrial content in gastrocnemius muscle and improves running endurance in sedentary C57BL/6J mice

The α-eleostearic acid (α-ESA) in bitter melon seed oil (BMSO) is efficiently converted by the body into rumenic acid. The objective of this study was to investigate effects of BMSO on skeletal muscle fiber-type switch and endurance capacity in mice, with or without exercise training. In a 3×2 factorial design, C57BL/6J mice were fed a 30% high-fat diet composed of soybean oil, butter or a 1:1 mixture of BMSO and soybean oil, i.e., SB, BT and BM diets, respectively, and were allocated to be sedentary or undergo exercise (Ex). The Ex groups received a 15-min training regimen on a motorized treadmill 5 times a week. After 3-week intervention, endurance capacity was evaluated (total running time and distance until exhaustion). Mice fed a BM diet had significantly less body fat, with increased muscle percentage and improved endurance capacity. Combining sedentary and Ex groups, mice fed a BM diet ran 33% longer and 50% further than those fed SB, or 25% longer and 36% further than those fed BT (P<.01). The BM-diet-increased gastrocnemius cytochrome c protein and mitochondrial DNA content was more prominent in sedentary than in trained mice. Histochemical staining shows sedentary BM-fed mice had a higher succinate dehydrogenase activity among groups. Based on a reporter assay, rumenic acid, rather than α-ESA itself, activated PPARδ ligand binding domain. We concluded that BMSO improved endurance capacity via stimulation of mitochondrial biogenesis and function, potentially influencing muscle metabolism and fiber-type composition in sedentary mice.     

Antioxidant enzyme systems in rat liver and skeletal muscle. Influences of selenium deficiency, chronic training, and acute exercise

The influences of selenium deficiency (Se-D), chronic training, and an acute bout of exercise on hepatic and skeletal muscle antioxidant enzymes, i.e., superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX), as well as glutathione S-transferase (GST) and tissue lipid peroxidation, were investigated in post-weaning male Sprague-Dawley rats. Se-D per se depleted GPX in both liver and skeletal muscle but had no effect on SOD or catalase activity. One hour of treadmill running (20 m/min, 0% grade and 27 m/min, 15% grade for untrained and trained rats, respectively) significantly elevated hepatic catalase and cytosolic SOD activity; more prominent activations were found in the Se-D or untrained rats, whereas skeletal muscle antioxidant enzymes were little affected. Ten weeks of training (1 h/day, 5 days/week at 27 m/min, 15% grade) increased hepatic mitochondrial SOD by 23% (P less than 0.05) in Se-D rats. Both hepatic mitochondrial and cytosolic GPX were decreased by training whereas GPX was increased twofold in skeletal muscle mitochondria. Se-independent GPX was elevated by training only in the skeletal muscle mitochondria of Se-D rats. Lipid peroxidation (malondialdehyde formation) was increased by an acute bout of exercise in hepatic mitochondria of the untrained rats and in skeletal muscle mitochondria of the Se-D rats. These data indicate that antioxidant enzymes in liver and skeletal muscle are capable of adapting to selenium deficiency and exercise to minimize oxidative injury caused by free radicals.     

The effects of swimming and running regimens on skeletal muscle glycogen in the rat.

Endurance capacity and the effects of different post-exercise states on skeletal muscle glycogen have been studied in rats trained by swimming or running and in sedentary controls. Regular endurance exercise resulted in increased skeletal muscle glycogen stores. A greater depletion was observed in trained animals than in non-trained animals after a training bout or exhaustive exercise. While muscle glycogen levels did not reflect a differential training stimulus (running vs swimming), swimming as a measure of exhaustive exercise was deemed invalid because of the ability of trained swimmers to avoid stenuous exercise by an alteration of swimming pattern.     

Lipid peroxidation and scavenger enzymes during exercise: adaptive response to training

This study was designed to determine whether endurance training would influence the production of lipid peroxidation (LI-POX) by-products as indicated by malondialdehyde (MDA) at rest and after an acute exercise run. Additionally, the scavenger enzymes catalase (CAT) and superoxide dismutase (SOD) were examined to determine whether changes in LIPOX are associated with alterations in enzyme activity both at rest and after exercise. Male Sprague-Dawley rats (n = 32) were randomly assigned to either trained or sedentary groups and were killed either at rest or after 20 min of treadmill running. The training program increased oxidative capacity 64% in leg muscle. After exercise, the sedentary group demonstrated increased LIPOX levels in liver and white skeletal muscle, whereas the endurance-trained group did not show increases in LIPOX after exercise. CAT activity was higher in both red and white muscle after exercise in the trained animals. Total SOD activity was unaffected by either acute or chronic exercise. These data suggest that endurance training can result in a reduction in LIPOX levels as indicated by MDA during moderate-intensity exercise. It is possible that activation of the enzyme catalase and the increase in respiratory capacity were contributory factors responsible for regulating LIPOX after training during exercise.     

Changes in skeletal muscle in males and females following endurance training

Gender differences in substrate selection have been reported during endurance exercise. To date, no studies have looked at muscle enzyme adaptations following endurance exercise training in both genders. We investigated the effect of a 7-week endurance exercise training program on the activity of beta-oxidation, tricarboxylic acid cycle and electron transport chain enzymes, and fiber type distribution in males and females. Training resulted in an increase in VO2peak, for both males and females of 17% and 22%, respectively (P < 0.001). The following muscle enzyme activities increased similarly in both genders: 3-beta-hydroxyacyl CoA dehydrogenase (38%), citrate synthase (41%), succinate-cytochrome c oxidoreductase (41%), and cytochrome c oxidase (COX; 26%). The increase in COX activity was correlated (R2 = 0.52, P < 0.05) with the increase in VO2peak/fat free mass. Fiber area, size, and % area were not affected by training for either gender, however, males had larger Type II fibers (P < 0.05) and females had a greater Type I fiber % area (P < 0.05). Endurance training resulted in similar increases in skeletal muscle oxidative potential for both males and females. Training did not affect fiber type distribution or size in either gender.     

Skeletal muscle changes after endurance training at high altitude.

The effects of endurance training on the skeletal muscle of rats have been studied at sea level and simulated high altitude (4,000 m). Male Wistar rats were randomly assigned to one of four groups: exercise at sea level, exercise at simulated high altitude, sedentary at sea level, and sedentary at high altitude (n = 8 in each group). Training consisted of swimming for 1 h/day in water at 36 degrees C for 14 wk. Training and exposure to a high-altitude environment produced a decrease in body weight (P less than 0.001). There was a significant linear correlation between muscle mass and body weight in the animals of all groups (r = 0.89, P less than 0.001). High-altitude training enhanced the percentage of type IIa fibers in the extensor digitorum longus muscle (EDL, P less than 0.05) and deep portions of the plantaris muscle (dPLA, P less than 0.01). High-altitude training also increased the percentage of type IIab fibers in fast-twitch muscles. These muscles showed marked metabolic adaptations: training increased the activity levels of enzymes involved in the citric acid cycle (citrate synthase, CS) and the beta-oxidation of fatty acids (3 hydroxyacyl CoA dehydrogenase, HAD). This increase occurred mainly at high altitude (36 and 31% for HAD in EDL and PLA muscles; 24 and 31% for CS in EDL and PLA muscles). Training increased the activity of enzymes involved in glucose phosphorylation (hexokinase). High-altitude training decreased lactate dehydrogenase activity. Endurance training performed at high altitude and sea level increased the isozyme 1-to-total lactate dehydrogenase activity ratio to the same extent.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise early in life in rats born small does not normalize reductions in skeletal muscle PGC-1α in adulthood

We have previously shown that 4 wk of exercise training early in life normalizes the otherwise greatly reduced pancreatic β-cell mass in adult male rats born small. The aim of the current study was to determine whether a similar normalization in adulthood of reduced skeletal muscle mitochondrial biogenesis markers and alterations in skeletal muscle lipids of growth-restricted male rats occurs following early exercise training. Bilateral uterine vessel ligation performed on day 18 of gestation resulted in Restricted offspring born small (P < 0.05) compared with both sham-operated Controls and a sham-operated Reduced litter group. Offspring remained sedentary or underwent treadmill running from 5-9 (early exercise) or 20-24 (later exercise) wk of age. At 24 wk of age, Restricted and Reduced litter offspring had lower (P < 0.05) skeletal muscle peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) protein expression compared with Control offspring. Early exercise training had the expected effect of increasing skeletal muscle markers of mitochondrial biogenesis, but, at this early age (9 wk), there was no deficit in Restricted and Reduced litter skeletal muscle mitochondrial biogenesis. Unlike our previous observations in pancreatic β-cell mass, there was no "reprogramming" effect of early exercise on adult skeletal muscle such that PGC-1α was lower in adult Restricted and Reduced litter offspring irrespective of exercise training. Later exercise training increased mitochondrial biogenesis in all groups. In conclusion, although the response to exercise training remains intact, early exercise training in rats born small does not have a reprogramming effect to prevent deficits in skeletal muscle markers of mitochondrial biogenesis in adulthood.     

Effects of continuous low-carbohydrate diet after long-term exercise on GLUT-4 protein content in rat skeletal muscle.

Stimulation of AMPK and decreased glycogen levels in skeletal muscle have a deep involvement in enhanced insulin action and GLUT-4 protein content after exercise training. The present study examined the chronic effects of a continuous low-carbohydrate diet after long-term exercise on GLUT-4 protein content, glycogen content, AMPK, and insulin signaling in skeletal muscle. Rats were divided randomly into four groups: normal chow diet sedentary (N-Sed), low carbohydrate diet sedentary (L-Sed), normal chow diet exercise (N-Ex), and low carbohydrate diet exercise (L-Ex) groups. Rats in the exercise groups (N-Ex and L-Ex) were exercised by swimming for 6 hours/day in two 3-hour bouts separated by 45 minutes of rest. The 10-day exercise training resulted in a significant increase in the GLUT-4 protein content (p<0.01). Additionally, the GLUT-4 protein content in L-Ex rats was increased by 29% above that in N-Ex rats (p<0.01). Finally, the glycogen content in skeletal muscle of L-Ex rats was decreased compared with that of N-Ex rats. Taken together, we suggest that the maintenance of glycogen depletion after exercise by continuous low carbohydrate diet results in the increment of the GLUT-4 protein content in skeletal muscle.     

Cytochrome c protein synthesis rate in rat skeletal muscle.

Endurance training is associated with increases in mitochondrial density, of which cytochrome c protein is an index. Increases in the synthesis rates of cytochrome c protein in skeletal muscle during endurance training have been inferred (Biochem. Biophys. Res. Commun. 66: 173, 1975; J. Biol. Chem. 252: 416, 1977). One purpose of the present study was to test these indirect approximations with direct measurements of the synthesis rates of cytochrome c protein in skeletal muscles postexercise. No change in the fractional synthesis rate of cytochrome c was detected in the red quadriceps muscle of rats either 2-7 h after a 104-min run on a motor-driven treadmill or 17-22 h after the final bout of 4 days of running 100 min/day. If the 16% increase in cytochrome c protein concentration in the red quadriceps muscle on the 5th day of training is used to calculate the nanomoles of cytochrome c synthesized per gram of wet muscle weight, the normalized rate of cytochrome c protein synthesis is increased 29% on the 5th day of training. The observation of no significant alteration in cytochrome c mRNA in the red quadriceps muscle of rats during the 1st wk of training implies that the initial increase in the synthesis rate of cytochrome c protein normalized per unit of muscle mass during treadmill training is likely to occur at a translational or posttranslational step. These results suggest that the control of increased cytochrome c expression in skeletal muscle during exercise training involves a complex mechanism.     

Exercise reverses high-fat diet-induced impairments on compartmentalization and activation of components of the insulin-signaling cascade in skeletal muscle

The aims of this investigation were 1) to determine whether endurance exercise training could reverse impairments in insulin-stimulated compartmentalization and/or activation of aPKCzeta/lambda and Akt2 in skeletal muscle from high-fat-fed rodents and 2) to assess whether the PPARgamma agonist rosiglitazone could reverse impairments in skeletal muscle insulin signaling typically observed after high-fat feeding. Sprague-Dawley rats were placed on chow (NORCON, n = 16) or high-fat (n = 64) diets for 4 wk. During a subsequent 4-wk experimental period, high-fat-fed rats were allocated (n = 16/group) to either sedentary control (HFC), exercise training (HFX), rosiglitazone treatment (HFRSG), or a combination of both exercise training and rosiglitazone (HFRX). Following the 4-wk experimental period, animals underwent hindlimb perfusions. Insulin-stimulated plasma membrane-associated aPKCzeta and -lambda protein concentration, aPKCzeta/lambda activity, GLUT4 protein concentration, cytosolic Akt2, and aPKCzeta/lambda activities were reduced (P < 0.05) in HFC compared with NORCON. Cytosolic Akt2, aPKCzeta, and aPKClambda protein concentrations were not affected in HFC compared with NORCON. Exercise training reversed the deleterious effects of the high-fat diet such that insulin-stimulated compartmentalization and activation of components of the insulin-signaling cascade in HFX were normalized to NORCON. High-fat diet-induced impairments to skeletal muscle glucose metabolism were not reversed by rosiglitazone administration, nor did rosiglitazone augment the effect of exercise. Our findings indicate that chronic exercise training, but not rosiglitazone, reverses high-fat diet induced impairments in compartmentalization and activation of components of the insulin-signaling cascade in skeletal muscle.     

Dietary Fat Type and Regular Exercise Affect Mitochondrial Composition and Function Depending on Specific Tissue in the Rat

Physical exercise and fatty acids have been studied in relation to mitochondrial composition and function in rat liver, heart, and skeletal muscle. Male rats were divided into two groups according to dietary fat type (virgin olive and sunflower oils). One-half of the animals from each group were subjected to a submaximal exercise for 8 weeks; the other half acted as sedentary controls. Coenzyme Q, cytochromes b, c + c1, a + a3 concentrations, and the activity of cytochrome c oxidase were determined. Regular exercise increased (P < 0.05) the concentration of the above-mentioned elements and the activity of the cytochrome c oxidase by roughly 50% in liver and skeletal muscle. In contrast, physical exercise decreased (P < 0.05) cytochrome c oxidase activity in the heart (in micromol/min/g, from 8.4+/-0.1 to 4.9+/-0.1 in virgin olive oil group and from 9.7+/-0.1 to 6.7+/-0.2 in sunflower oil animals). Dietary fat type raised the levels of coenzyme Q, cytochromes, and cytochrome c oxidase activity in skeletal muscle (P < 0.05) among the rats fed sunflower oil. In conclusion, dietary fat type, regular exercise, and the specific tissue modulate composition and function of rat mitochondria.     

Effect of anabolic steroids on mitochondria and sarcotubular system of skeletal muscle.

Soleus and extensor digitorum longus (EDL) mitochondria and sarcotubular system were examined in sedentary and trained (treadmill for 12 wk) male rats that were treated with fluoxymesterone or methandrostanolone (2 mg/kg, 5 days/wk, for 8 wk). Neither physical exercise nor anabolic/androgenic steroid administration resulted in a significant change in muscle wet weight. Treatment with the anabolizing androgens increased succinate dehydrogenase activity in fast-twitch muscle mitochondria; this effect was not enhanced by training and was not observed in soleus mitochondria. On the other hand, the content of the slow-twitch muscle in sarcotubular fraction was increased in sedentary rats by fluoxymesterone or methandrostanolone treatment, whereas no significant changes were found in EDL. The training program affected adenosinetriphosphatase (ATPase) activities in the sarcotubular fraction; Mg2(+)-ATPase was increased in both soleus and EDL, but Ca2(+)-ATPase was decreased only in soleus. However, in sedentary animals only the Mg2(+)-dependent activity of EDL was increased by anabolizing androgen treatment, and this change was not potentiated by additional training. The present data indicate that anabolic/androgenic steroids can affect mitochondrial and sarcotubular enzymes in skeletal muscle. The effects are muscle-type specific.     

Adaptive response of hypertrophied skeletal muscle to endurance training

The response of hypertrophied soleus and plantaris muscle of rats to endurance training was studied. Hypertrophy was produced by bilateral extirpation of the gastrocnemius muscle. A 13-wk training program of treadmill running initiated 30 days after removal of the gastrocnemius muscle accentuated (P less than 0.01) the hypertrophy. Succinate dehydrogenase activities of the enlarged muscles of sedentary rats were similar to those of normal animals, as were the increases associated with training. Phosphorylase and hexokinase activities were unaltered as a result of the experimental perturbations. Rates of glycogen depletion during exercise were lower (P less than 0.01) in the liver and soleus and plantaris muscles of endurance-trained animals. No difference existed in the rate of glycogen depletion of normal and hypertrophied muscle within the sedentary or trained groups. These data demonstrate that extensively hypertrophied muscle responds to training and exercise in a manner similar to that of normal muscle.     

Interactive effects of anemia and muscle oxidative capacity on exercise endurance

We used endurance training and acute anemia to assess the interactions among maximal oxygen consumption (VO2max), muscle oxidative capacity, and exercise endurance in rats. Animals were evaluated under four conditions: untrained and endurance-trained with each group subdivided into anemic (animals with reduced hemoglobin concentrations) and control (animals with unchanged hemoglobin concentrations). Anemia was induced by isovolemic plasma exchange transfusion. Hemoglobin concentration and hematocrit were decreased by 38 and 41%, respectively. Whole body VO2max was decreased by 18% by anemia regardless of training condition. Anemia significantly reduced endurance by 78% in untrained rats but only 39% in trained animals. Endurance training resulted in a 10% increase in VO2max, a 75% increase in the distance run to exhaustion, and 35, 45, and 58% increases in skeletal muscle pyruvate-malate, alpha-ketoglutarate, and palmitylcarnitine oxidase activities, respectively. We conclude that endurance is related to the interactive effects of whole body VO2max and muscle oxidative capacities for the following reasons: 1) anemic untrained and trained animals had similar VO2max but trained rats had higher muscle oxidative capacities and greater endurance; 2) regardless of training status, the effect of acute anemia was to decrease VO2max and endurance; and 3) trained anemic rats had lower VO2max but had greater muscle oxidative capacity and greater endurance than untrained controls.     

Endurance training partially reverses dietary-induced leptin resistance in rodent skeletal muscle

Leptin acutely stimulates skeletal muscle fatty acid (FA) metabolism in lean rodents and humans. This stimulatory effect is eliminated following the feeding of high-fat diets in rodents as well as in obese humans. The mechanism(s) responsible for the development of skeletal muscle leptin resistance is unknown; however, a role for increased suppressor of cytokine signaling-3 (SOCS3) inhibition of the leptin receptor has been demonstrated in other rodent tissues. Furthermore, whether exercise intervention is an effective strategy to prevent or attenuate the development of skeletal muscle leptin resistance has not been investigated. Toward this end, 48 Sprague-Dawley rats (175-190 g; approximately 2-3 mo of age) were fed control or high-fat (60% kcal) diets for 4 wk and either remained sedentary or were treadmill trained. In control diet-fed animals that remained sedentary (CS) or were endurance trained (CT), leptin stimulated FA oxidation (CS +32 +/- 15%, CT +30 +/- 17%; P < 0.05), suppressed triacylglycerol (TAG) esterification (CS -17 +/- 7%, CT -24 +/- 8%; P < 0.05), and reduced the esterification-to-oxidation ratio (CS -19 +/- 13%, CT -29 +/- 10%; P < 0.001) in soleus muscle. High-fat feeding induced leptin resistance in the soleus of sedentary rats (FS), whereas endurance exercise training (FT) restored the ability of leptin to suppress TAG esterification (-19 +/- 9%, P = 0.038). Training did not completely restore the ability of leptin to stimulate FA oxidation. High-fat diets stimulated SOCS3 mRNA expression irrespective of training status (FS +451 +/- 120%, P = 0.024; FT +381 +/- 141%, P = 0.023). Thus the development of skeletal muscle leptin resistance appears to involve an increase in SOCS3 mRNA expression. Endurance training was generally effective in preventing the development of leptin resistance, although this did not appear to require a decrease in SOCS3 expression. Future studies should examine changes in the actual protein content of SOCS3 in muscle and establish whether aerobic exercise is also effective in treating leptin resistance in humans.     

Skeletal muscle type comparison of pyruvate dehydrogenase phosphatase activity and isoform expression: effects of obesity and endurance training

Pyruvate dehydrogenase (PDH) plays an important role in regulating carbohydrate metabolism in skeletal muscle. PDH is activated by PDH phosphatase (PDP) and deactivated by PDH kinase (PDK). Obesity has a large negative impact on skeletal muscle carbohydrate metabolism, whereas endurance training has been shown to improve regulatory control of skeletal muscle carbohydrate metabolism, more so when coupled with obesity. A majority of this literature has focused on PDK, with little information available on PDP. To determine the relative role of PDP in regulating skeletal muscle PDH activity with obesity and endurance training, obese and lean Zucker rats remained sedentary or were endurance trained (1 h/day, 5 days/wk) for a period of 8 wk. Soleus, red gastrocnemius, (RG), and white gastrocnemius (WG) muscles were sampled after the training period. The main findings were 1) obesity resulted in a 46% decrease in PDP activity expressed per milligram extracted mitochondrial protein only in RG, while PDP isoform content was unchanged; 2) 8 wk of endurance training led to a significant 1.4-2.2-fold increase in PDP activity of all muscle examined from obese rats, and the concomitant increase in PDP1 protein was only seen in soleus and RG; 3) 8 wk of endurance training led to a trending 1.4-2.2-fold increase in PDP activity of all muscle examined from obese rats, and the concomitant increase in PDP1 protein was only seen in soleus and RG; and 4) PDP2 protein content was not affected by obesity or training. These results suggest that decreased PDP activity in oxidative skeletal muscles may play a role in the impairment of carbohydrate metabolism in obese rats, which is reversible with endurance training.