High Capacity Running Research Articles

Low Intrinsic Aerobic Capacity Limits Recovery Response to Hindlimb Ischemia.

Introduction: In this study, we determined the influence of intrinsic exercise capacity on the vascular adaptive responses to hind limb ischemia. High Capacity Running, HCR; Low Capacity Running, LCR, rats were used to assess intrinsic aerobic capacity effects on adaptive responses to ischemia.Methods: Muscle samples from both ischemic and non-ischemic limb in both strains were compared, histologically for the muscle-capillary relationship, and functionally using microspheres to track blood flow and muscle stimulation to test fatigability. PCR was used to identify the differences in gene expression between the phenotypes following occlusive ischemia.Results: Prior to ligation, there were not significant differences between the phenotypes in the exhaustion time with high frequency pacing. Following ligation, LCR decreased significantly in the exhaustion time compare with HCRs (437 ± 47 vs. 824 ± 56, p < 0.001). The immediate decrease in flow was significantly more severe in LCRs than HCRs (52.5 vs. 37.8%, p < 0.001). VEGF, eNOS, and ANG2 (but not ANG1) gene expression were decreased in LCRs vs. HCRs before occlusion, and increased significantly in LCRs 14D after occlusion, but not in HCRs. LCR capillary density (CD) was significantly lower at all time points after occlusion (LCR 7D = 564.76 ± 40.5, LCR 14D = 507.48 ± 54.2, both p < 0.05 vs. HCR for respective time point). NCAF increased significantly in HCR and LCR in response to ischemia.Summary: These results suggest that LCR confers increased risk for ischemic injury and is subject to delayed and less effective adaptive response to ischemic stress.

Rats Genetically Selected for High Aerobic Exercise Capacity Have Elevated Plasma Bilirubin by Upregulation of Hepatic Biliverdin Reductase-A (BVRA) and Suppression of UGT1A1.

Exercise in humans and animals increases plasma bilirubin levels, but the mechanism by which this occurs is unknown. In the present study, we utilized rats genetically selected for high capacity running (HCR) and low capacity running (LCR) to determine pathways in the liver that aerobic exercise modifies to control plasma bilirubin. The HCR rats, compared to the LCR, exhibited significantly higher levels of plasma bilirubin and the hepatic enzyme that produces it, biliverdin reductase-A (BVRA). The HCR also had reduced expression of the glucuronyl hepatic enzyme UGT1A1, which lowers plasma bilirubin. Recently, bilirubin has been shown to activate the peroxisome proliferator-activated receptor-α (PPARα), a ligand-induced transcription factor, and the higher bilirubin HCR rats had significantly increased PPARα-target genes Fgf21, Abcd3, and Gys2. These are known to promote liver function and glycogen storage, which we found by Periodic acid–Schiff (PAS) staining that hepatic glycogen content was higher in the HCR versus the LCR. Our results demonstrate that exercise stimulates pathways that raise plasma bilirubin through alterations in hepatic enzymes involved in bilirubin synthesis and metabolism, improving liver function, and glycogen content. These mechanisms may explain the beneficial effects of exercise on plasma bilirubin levels and health in humans.

Myosin Heavy Chain Isoform Mrna Expression In Low- And High-capacity Running Rats

Differential expression of Myosin Heavy Chain (MHC) isoforms in skeletal muscle determines its metabolic and functional characteristics. Endurance exercise training is associated with fast-to-slow MHC isoform transition, and which is considered to mediate the beneficial effects of exercise on metabolic health. Rats genetically bred for low-capacity running (LCR) and high-capacity running (HCR) are characterized by the health benefits typically described after endurance exercise training. LCR and HCR rats differed in maximal running capacity 14 fold. PURPOSE: To quantify mRNA expression for slow (MHC-I) and fast (MCH-IIa, MCH-IIb) MHC isoforms in soleus, gastrocnemius and vastus skeletal muscle of LCR and HCR male adult rats, and determine if HCR rats have higher mRNA expression for slow, and lower mRNA expression for fast, MHC isoforms. METHODS: Muscle tissue from 5 HCR and 5 LCR rats was homogenized and mRNA was isolated. The mRNA content of MHC isoforms in muscle was quantified using reverse transcriptase polymerase chain reaction (RT-PCR), and standardized to the 18S mRNA content in muscle. Differences between groups were calculated using the comparative CT method (2-ΔΔCT). LCR were the control group. RESULTS: Expression of mRNA of the MHC isoforms differed between groups and the type of skeletal muscle analyzed. MHC-I mRNA expression was lower in the HCR compared to LCR across all muscle groups, but this difference (2-ΔΔCT) was more pronounced for the gastrocnemius muscle [LCR: 1.0 ± 0.6 (mean±SE); HCR: 0.3 ± 0.2; P = 0.08]. Although MHC-IIa mRNA expression appeared lower in soleus and vastus in the HCR, it was higher in the HCR compared to LCR in the gastrocnemius muscle [LCR: 1.0 ± 1.0; HCR: 4.6 ± 3.6; P = 0.07]. MHC-IIb mRNA expression was lower in the HCR compared to LCR across all muscle groups, but this difference was more pronounced for the soleus muscle [LCR: 1.0 ± 1.1; HCR: 0.2 ± 0.4; P = 0.08]. CONCLUSION: Genetic differences linked to the MHC transcriptome (i.e., decrease in MHC-I mRNA) in muscle do not explain the exercise performance observed in HCR rats. Changes in the muscle MHC transcriptome may not directly be responsible for the health benefits associated with exercise training. It remains to be determined on whether the differences we observed at the MHC mRNA level are translated to the MHC proteome level.

Abstract 122: Cardiac Hypertrophy and Vascular Function are Directly Proportional to Mitochondrial Variations in Intrinsic Exercise Capacity

Exercise is a primary lifestyle intervention to control cardiovascular diseases such as hypertension. Exercise capacity and its health benefits are inheritable. However, the mechanisms by which exercise capacity differences influence overall health state remain unclear. We first hypothesized that low and high intrinsic exercise capacity lead to distinct heart weight and vascular function. Animal model (male, 20-24-weeks old, n = 6): heterogeneous stock selectively bred for over 20 years to produce low-capacity running rats (LCR) and high-capacity running rats (HCR), and an intrinsic control, high response trainer rats (HRT, control). Statistics: t-test: *p&lt;0.05. Left ventricular (LV) weight was normalized by tibia length. We observed that HCR presented with LV hypertrophy compared to LCR and control (Control: 0.0155 ± 0.0006 vs. HCR: 0.0192 ± 0.0007* vs. LCR: 0.0164 ± 0.0004). Performing wire myography with 3 rd -order mesenteric resistance arteries (MRA), we observed that LCR MRA had an impaired maximum relaxation response (E max ) to acetylcholine (ACh) compared to HCR and control (Control: 94.99 ± 1.79 vs. HCR: 93.49 ± 12.17 vs. LCR: 72.95 ± 12.40*). Next, we questioned if these differences were the result of mitochondria. We used two reciprocal conplastic strains created by utilizing maternal mitochondrial inheritance (male, 30-36-weeks old, n = 4): LCR nuclear genome with HCR mitochondria (LCR.HCR mt ) and the reciprocal HCR.LCR mt . We observed that LCR.HCR mt presented with LV hypertrophy compared to LCR (0.0195 ± 0.0002* vs 0.0164 ± 0.0004) while HCR.LCR mt abolished HCR LV hypertrophy (0.0151 ± 0.0002* vs. 0.0192 ± 0.0007). Interestingly, in a separate group of animals (n = 4 - 5), LCR had higher mean arterial pressure (MAP) compared to HCR, and LCR.HCR mt had reduced MAP compared to LCR (LCR: 119 ± 2 vs. LCR.HCR mt : 111 ± 1*). No changes were observed in HCR.LCR mt compared to HCR. Further, LCR.HCR mt MRA presented with improved E max to ACh compared to LCR MRA (LCR: 72 ± 12 vs. LCR.HCR mt : 93 ± 2*) while no changes were observed in HCR.LCR mt MRA compared to HCR MRA. Overall, we conclude that intrinsic exercise capacity is directly proportional to cardiovascular effects. Similar to the nuclear genome, mitochondria are the key to this hereditary predisposition.

Intrinsic High Aerobic Capacity in Male Rats Protects Against Diet-Induced Insulin Resistance.

Low aerobic capacity increases the risk for insulin resistance but the mechanisms are unknown. In this study, we tested susceptibility to acute (3-day) high-fat, high-sucrose diet (HFD)-induced insulin resistance in male rats selectively bred for divergent intrinsic aerobic capacity, that is, high-capacity running (HCR) and low-capacity running (LCR) rats. We employed hyperinsulinemic-euglycemic clamps, tracers, and transcriptome sequencing of skeletal muscle to test whether divergence in aerobic capacity impacted insulin resistance through systemic and tissue-specific metabolic adaptations. An HFD evoked decreased insulin sensitivity and insulin signaling in muscle and liver in LCR rats, whereas HCR rats were protected. An HFD led to increased glucose transport in skeletal muscle (twofold) of HCR rats while increasing glucose transport into adipose depots of the LCR rats (twofold). Skeletal muscle transcriptome revealed robust differences in the gene profile of HCR vs LCR on low-fat diet and HFD conditions, including robust differences in specific genes involved in lipid metabolism, adipogenesis, and differentiation. HCR transcriptional adaptations to an acute HFD were more robust than for LCR and included genes driving mitochondrial energy metabolism. In conclusion, intrinsic aerobic capacity robustly impacts systemic and skeletal muscle adaptations to HFD-induced alterations in insulin resistance, an effect that is likely driven by baseline differences in oxidative capacity, gene expression profile, and transcriptional adaptations to an HFD.

Systemic Metabolomics and Mitochondrial Energetics in High- Compared to Low-Running Capacity Rats as a Function of Age

Exercise capacity during aging is strongly linked to life quality, morbidity and mortality. In a selectively-bred rat model of intrinsic aerobic phenotypes, low-capacity (LCR) compared to high-capacity running (HCR) rats exhibit increased rates of metabolic syndrome, adiposity, dyslipidemia, endothelial dysfunction, and insulin resistance. Previously, we showed that with aging HCR rats present greater mitochondrial turnover underlying higher cardiomyocyte energetic performance, sustained by preferential selection of lipids oxidation with improved control of acetyl-CoA (AcCoA) concentration. All these positive indexes decline with aging, but they are better preserved in HCR vs. LCR, parallel with healthier aging and extended longevity. To investigate systemic metabolism in main organs supplying substrates (fatty acids, glucose, ketone bodies) to the heart, untargeted metabolomics was performed in liver and serum of young and middle age female HCR and LCR rats. Multivariate statistics indicated a metabolome pattern in liver comprised by higher abundance of fatty acids (e.g., palmitic, palmitoleic, oleic) at similar levels of intermediates from glucose metabolism in HCR vs. LCR. As a function of age, the serum of HCR rats exhibited an enrichment in fatty acids (e.g., linoleic, palmitic, arachidic) consistent with the changes observed in liver's metabolome. Higher liver AMP levels in HCR vs. LCR suggest activation of AMPK signaling, in agreement with the enhanced autophagy/mitophagy observed in HCR. Importantly, the higher relative LCR/HCR fold-changes of acetylated intermediates, in both liver and serum, agrees with the idea of widespread increased acetylation, compatible with the higher concentration of AcCoA measured in cardiomyocytes from LCR vs. HCR. Metabolomics reveal systemic, organ-concerted (liver-serum-heart), metabolic remodeling compatible with higher energetic performance, better preserved mitochondrial turnover, preferential lipid oxidation, and improved control of acetylation in HCR leading to extended longevity and better functional capacity.

Systems-level computational modeling demonstrates fuel selection switching in high capacity running and low capacity running rats.

High capacity and low capacity running rats, HCR and LCR respectively, have been bred to represent two extremes of running endurance and have recently demonstrated disparities in fuel usage during transient aerobic exercise. HCR rats can maintain fatty acid (FA) utilization throughout the course of transient aerobic exercise whereas LCR rats rely predominantly on glucose utilization. We hypothesized that the difference between HCR and LCR fuel utilization could be explained by a difference in mitochondrial density. To test this hypothesis and to investigate mechanisms of fuel selection, we used a constraint-based kinetic analysis of whole-body metabolism to analyze transient exercise data from these rats. Our model analysis used a thermodynamically constrained kinetic framework that accounts for glycolysis, the TCA cycle, and mitochondrial FA transport and oxidation. The model can effectively match the observed relative rates of oxidation of glucose versus FA, as a function of ATP demand. In searching for the minimal differences required to explain metabolic function in HCR versus LCR rats, it was determined that the whole-body metabolic phenotype of LCR, compared to the HCR, could be explained by a ~50% reduction in total mitochondrial activity with an additional 5-fold reduction in mitochondrial FA transport activity. Finally, we postulate that over sustained periods of exercise that LCR can partly overcome the initial deficit in FA catabolic activity by upregulating FA transport and/or oxidation processes.

Aerobic capacity and hepatic mitochondrial lipid oxidation alters susceptibility for chronic high-fat diet-induced hepatic steatosis.

Rats selectively bred for high capacity running (HCR) or low capacity running (LCR) display divergence for intrinsic aerobic capacity and hepatic mitochondrial oxidative capacity, both factors associated with susceptibility for nonalcoholic fatty liver disease. Here, we tested if HCR and LCR rats display differences in susceptibility for hepatic steatosis after 16 wk of high-fat diets (HFD) with either 45% or 60% of kcals from fat. HCR rats were protected against HFD-induced hepatic steatosis, whereas only the 60% HFD induced steatosis in LCR rats, as marked by a doubling of liver triglycerides. Hepatic complete fatty acid oxidation (FAO) and mitochondrial respiratory capacity were all lower in LCR compared with HCR rats. LCR rats also displayed lower hepatic complete and incomplete FAO in the presence of etomoxir, suggesting a reduced role for noncarnitine palmitoyltransferase-1-mediated lipid catabolism in LCR versus HCR rats. Hepatic complete FAO and mitochondrial respiration were largely unaffected by either chronic HFD; however, 60% HFD feeding markedly reduced 2-pyruvate oxidation, a marker of tricarboxylic acid (TCA) cycle flux, and mitochondrial complete FAO only in LCR rats. LCR rats displayed lower levels of hepatic long-chain acylcarnitines than HCR rats but maintained similar levels of hepatic acetyl-carnitine levels, further supporting lower rates of β-oxidation, and TCA cycle flux in LCR than HCR rats. Finally, only LCR rats displayed early reductions in TCA cycle genes after the acute initiation of a HFD. In conclusion, intrinsically high aerobic capacity confers protection against HFD-induced hepatic steatosis through elevated hepatic mitochondrial oxidative capacity.

Increased aerobic capacity reduces susceptibility to acute high-fat diet-induced weight gain.

Aerobic capacity is the most powerful predictor of all-cause mortality in humans; however, its role in the development of obesity and susceptibility for high-fat diet (HFD)-induced weight gain is not completely understood. Herein, a rodent model system of divergent intrinsic aerobic capacity [high capacity running (HCR) and low capacity running (LCR)] was utilized to evaluate the role of aerobic fitness on 1-week HFD-induced (45% and 60% kcal) weight gain. Food/energy intake, body composition analysis, and brown adipose tissue gene expression were assessed as important potential factors involved in modulating HFD-induced weight gain. HCR rats had reduced 1-week weight gain on both HFDs compared with LCR. Reduced HFD-induced weight gain was associated with greater adaptability to decrease food intake following initiation of the HFDs. Further, the HCR rats were observed to have reduced feeding efficiency and greater brown adipose mass and expression of genes involved in thermogenesis. Rats with high intrinsic aerobic capacity have reduced susceptibility to 1-week HFD-induced weight gain, which is associated with greater food intake adaptability to control intake of energy-dense HFDs, reduced weight gain per kcal consumed, and greater brown adipose tissue mass and thermogenic gene expression.

Ovariectomized Highly Fit Rats Are Protected against Diet-Induced Insulin Resistance.

In the absence of exercise training, rats selectively bred for high intrinsic aerobic capacity (high-capacity running (HCR)) are protected against ovariectomy (OVX)-induced insulin resistance (IR) and obesity compared with those bred for low intrinsic aerobic capacity (low-capacity running (LCR)). This study determined whether OVX HCR rats remain protected with exposure to high-fat diet (HFD) compared with OVX LCR rats. Female HCR and LCR rats (n = 36; age, 27-33 wk) underwent OVX and were randomized to a standard chow diet (NC, 5% kcal fat) or HFD (45% kcal fat) ad libitum for 11 wk. Total energy expenditure, resting energy expenditure, spontaneous physical activity (SPA), and glucose tolerance were assessed midway, whereas fasting circulating metabolic markers, body composition, adipose tissue distribution, and skeletal muscle adenosine monophosphate-activated protein kinase (AMPK), and mitochondrial markers were assessed at sacrifice. Both HCR and LCR rats experienced HFD-induced increases in total and visceral adiposity after OVX. Despite similar gains in adiposity, HCR rats were protected from HFD-induced IR and reduced total energy expenditure observed in LCR rats (P < 0.05). This metabolic protection was likely attributed to a compensatory increase in SPA and associated preservation of skeletal muscle AMPK activity in HCR; however, HFD significantly reduced SPA and AMPK activity in LCR (P < 0.05). In both lines, HFD reduced citrate synthase activity, gene expression of markers of mitochondrial biogenesis (tFAM, NRF1, and PGC-1α), and protein levels of mitochondrial oxidative phosphorylation complexes I, II, IV, and V in skeletal muscle (all P < 0.05). After OVX, HCR and LCR rats differentially respond to HFD such that HCR increase while LCR decrease SPA. This "physical activity compensation" likely confers protection from HFD-induced IR and reduced energy expenditure in HCR rats.

Reduced Short‐chain Fatty Acid Producing Microbiota are Linked to Increased Energy Intake and Susceptibility to High Fat Diet Induced Hepatic Steatosis in Low Aerobic Capacity Rats

Poor aerobic fitness is linked to nonalcoholic fatty liver disease and increased all‐cause mortality. We have previously shown that low aerobically fit, low capacity running (LCR) rats fed an acute high fat diet (HFD; 45% kcal from fat) for 3 days displayed a greater positive energy balance due to a greater increase in energy intake and reduced energy expenditure, which likely played a role in their susceptibility for hepatic steatosis compared with high aerobically fit, high capacity running (HCR) rats. Here, we tested the hypothesis that poor physiological outcomes in LCR rats following acute HFD feeding are associated with alterations in cecal microbiota. Through amplification of the V4 region of bacterial 16S rDNA, we found that at the phylum level, the LCR rats had a reduced relative abundance of cecal Proteobacteria (P&lt;0.05) and increased Cyanobacteria (P&lt;0.05) compared with HCR rats. Interestingly within Proteobacteria, Desulfovibrionaceae, and unassigned genera within Desulfovibrionaceae, were increased (P&lt;0.05) in HCR compared with LCR rats, suggesting increased sulfur reduction from endogenous substrates (i.e. mucins and proteins). Conversely, the Proteobacteria family Alcaligenaceae was increased (P&lt;0.05) in LCR compared with HCR rats, which may be related to susceptibility to NAFLD in the LCR rats. While acute HFD feeding reduced the overall relative abundance of Firmicutes in both strains, short‐chain fatty acid (SCFA)‐producing Phascolarctobacterium and Butyricimonas were reduced (P&lt;0.05) only in the LCR rats. In addition, SCFA‐producing Ruminococcae (r=−0.75) and Ruminococcus (r=−0.73, P&lt;0.01) were negatively correlated with energy intake only in the LCR rats. Overall, these data suggest that the susceptibility to acute HFD‐induced increases in energy intake and hepatic steatosis in low aerobically fit animals is associated with changes in the cecal microbiome, particularly suppression of SCFA‐producing bacteria.Support or Funding InformationAHA 14POST20110034 (EMM), NIH R01DK088940 (JPT), P40OD021331 and R01DK099034 (LGK and SLB), USDA‐CRIS 6206‐51000‐007‐00D‐05 (KS), VA‐CDA2 IK2BX001299 (RSR).

Effects of ovariectomy and intrinsic aerobic capacity on tissue-specific insulin sensitivity.

High-capacity running (HCR) rats are protected against the early (i.e., ∼ 11 wk postsurgery) development of ovariectomy (OVX)-induced insulin resistance (IR) compared with low-capacity running (LCR) rats. The purpose of this study was to utilize the hyperinsulinemic euglycemic clamp to determine whether 1) HCR rats remain protected from OVX-induced IR when the time following OVX is extended to 27 wk and 2) tissue-specific glucose uptake differences are responsible for the protection in HCR rats under sedentary conditions. Female HCR and LCR rats (n = 40; aged ∼ 22 wk) randomly received either OVX or sham (SHM) surgeries and then underwent the clamp 27 wk following surgeries. [3-(3)H]glucose was used to determine glucose clearance, whereas 2-[(14)C]deoxyglucose (2-DG) was used to assess glucose uptake in skeletal muscle, brown adipose tissue (BAT), subcutaneous white adipose tissue (WAT), and visceral WAT. OVX decreased the glucose infusion rate and glucose clearance in both lines, but HCR had better insulin sensitivity than LCR (P < 0.05). In both lines, OVX significantly reduced glucose uptake in soleus and gastrocnemius muscles; however, HCR showed ∼ 40% greater gastrocnemius glucose uptake compared with LCR (P < 0.05). HCR also exhibited greater glucose uptake in BAT and visceral WAT compared with LCR (P < 0.05), yet these tissues were not affected by OVX in either line. In conclusion, OVX impairs insulin sensitivity in both HCR and LCR rats, likely driven by impairments in insulin-mediated skeletal muscle glucose uptake. HCR rats have greater skeletal muscle, BAT, and WAT insulin-mediated glucose uptake, which may aid in protection against OVX-associated insulin resistance.

Divergent role of nitric oxide in insulin-stimulated aortic vasorelaxation between low- and high-intrinsic aerobic capacity rats

Low-intrinsic aerobic capacity is associated with increased risk for cardiovascular and metabolic diseases and is a strong predictor of early mortality. The effects of intrinsic aerobic capacity on the vascular response to insulin are largely unknown. We tested the hypothesis that rats selectively bred for a low capacity to run (LCR) exhibit vascular dysfunction and impaired vascular reactivity to insulin compared to high capacity running (HCR) rats. Mature female LCR (n = 21) and HCR (n = 17) rats were maintained under sedentary conditions, and in vitro thoracic aortic vascular function was assessed. LCR exhibited greater body mass (13%), body fat (35%), and subcutaneous, perigonadal, and retroperitoneal adipose tissue mass, than HCR. During an intraperitoneal glucose tolerance test, glucose area under the curve (AUC) was not different but insulin AUC was 2-fold greater in LCR than HCR. Acetylcholine and insulin-stimulated aortic vasorelaxation was significantly greater in LCR (65.2 ± 3.8%, and 32.7 ± 4.1%) than HCR (55.0 ± 3.3%, and 16.7 ± 2.8%). Inhibition of nitric oxide synthase (NOS) with L-NAME entirely abolished insulin-mediated vasorelaxation in the aorta of LCR, with no effect in HCR. LCR rats exhibited greater expression of Insulin Receptor protein, lower Endothelin Receptor-A protein, a down-regulation of transcripts for markers of immune cell infiltration (CD11C, CD4, and F4/80) and up-regulation of pro-atherogenic inflammatory genes (VCAM-1 and MCP-1) in the aorta wall. Contrary to our hypothesis, low-aerobic capacity was associated with enhanced aortic endothelial function and NO-mediated reactivity to insulin, despite increased adiposity and evidence of whole body insulin resistance.

Uphill running does not exacerbate collagenase-induced pathological changes in the Achilles tendon of rats selectively bred for high-capacity running

The Achilles tendon is a frequent site for degeneration, and advanced understanding of this pathology requires an animal model that replicates the human condition. The aim of this study was to explore whether intratendinous collagenase injection combined with treadmill running created a pathology in the rat Achilles tendon consistent with human Achilles tendinosis. Collagenase was injected into one Achilles tendon of 88 high-capacity running (HCR) rats, which were randomized into treadmill running and cage control groups. Running animals ran at speeds up to 30 m/min on a treadmill at a 15° incline for up to 1 h/d, 5 d/week for 4 or 10 weeks. Cage control animals maintained cage activity. Collagenase induced molecular, histopathological and mechanical changes within the Achilles tendon at 4 weeks. The mechanical changes persisted at 10 weeks; however, the histopathological and majority of the molecular changes were no longer present at 10 weeks. Treadmill running had minimal effect and did not exacerbate the collagenase-induced changes as there were no statistical interactions between the interventions. These data suggest combined intratendinous collagenase injection and treadmill running does not create pathology within the Achilles tendon of rats selectively bred for HCR that is consistent with human Achilles tendinosis.

THE EFFECTS OF UPHILL TREADMILL RUNNING AND COLLAGENASE ON RODENT ACHILLES TENDONS

IntroductionOveruse conditions of the Achilles tendon likely develop due to a combination of extrinsic and intrinsic risk factors. The purpose of this study was to investigate the individual and combined...

Uphill treadmill running does not induce histopathological changes in the rat Achilles tendon

BackgroundThe purpose of this study was to investigate whether uphill treadmill running in rats created histopathological changes within the Achilles tendon consistent with Achilles tendinosis in humans.MethodsTwenty-six mature rats selectively bred for high-capacity running were divided into run and cage control groups. Run group rats ran on a treadmill at a 15° incline for a maximum duration of 1 hr/d, 5 d/wk for 9 weeks at increasing speeds, while rats in the cage control group maintained normal cage activity. After 9 weeks, Achilles tendons were harvested for histological processing and semi-quantitative histopathological analysis.ResultsThere were no significant group differences within each of the individual histopathological categories assessed (all p ≥ 0.16) or for total histopathological score (p = 0.14).ConclusionsUphill treadmill running in rats selectively bred for high-capacity running did not generate Achilles tendon changes consistent with the histopathological presentation of Achilles tendinosis in humans.

Spontaneous activity, economy of activity, and resistance to diet-induced obesity in rats bred for high intrinsic aerobic capacity

Though obesity is common, some people remain resistant to weight gain even in an obesogenic environment. The propensity to remain lean may be partly associated with high endurance capacity along with high spontaneous physical activity and the energy expenditure of activity, called non-exercise activity thermogenesis (NEAT). Previous studies have shown that high-capacity running rats (HCR) are lean compared to low-capacity runners (LCR), which are susceptible to cardiovascular disease and metabolic syndrome. Here, we examine the effect of diet on spontaneous activity and NEAT, as well as potential mechanisms underlying these traits, in rats selectively bred for high or low intrinsic aerobic endurance capacity. Compared to LCR, HCR were resistant to the sizeable increases in body mass and fat mass induced by a high-fat diet; HCR also had lower levels of circulating leptin. HCR were consistently more active than LCR, and had lower fuel economy of activity, regardless of diet. Nonetheless, both HCR and LCR showed a similar decrease in daily activity levels after high-fat feeding, as well as decreases in hypothalamic orexin-A content. The HCR were more sensitive to the NEAT-activating effects of intra-paraventricular orexin-A compared to LCR, especially after high-fat feeding. Lastly, levels of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) in the skeletal muscle of HCR were consistently higher than LCR, and the high-fat diet decreased skeletal muscle PEPCK-C in both groups of rats. Differences in muscle PEPCK were not secondary to the differing amount of activity. This suggests the possibility that intrinsic differences in physical activity levels may originate at the level of the skeletal muscle, which could alter brain responsiveness to neuropeptides and other factors that regulate spontaneous daily activity and NEAT.