Acylcarnitine profile in Alaskan sled dogs during submaximal multiday exercise points out metabolic flexibility and liver role in energy metabolism.
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ABSTRACT:
SUBMITTER: Tosi I
PROVIDER: S-EPMC8360531 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background: Muscle responses to exercise are complex, and potentially include acute responses to exercise-induced injury as well as longer-term adaptive training responses. Using Alaskan sled dogs as an experimental model, changes in muscle gene expression were analyzed to better understand the temporal changes that occur after severe exercise. Methods: Dogs were randomly assigned to undertake in a 160 km run (n=9), or to remain at rest (n=4). Biceps femoris muscle was obtained by needle biopsy from the unexercised dogs and two dogs at each of 2, 6 and 12 hours after the exercise and from 3 dogs 24 hours after exercise. RNA was extracted and microarray analysis used to define gene transcriptional changes. Results: Nine hundred sixty three transcripts exhibited statistically significant change over time after exercise as compared to the unexercised dogs. The changes in gene expression after exercise occurred in a clear temporal pattern and included transcripts with increased expression 2 hours after exercise with a return towards resting levels by 6 hours after exercise. Other transcripts demonstrated increased expression which peaked at six hours after exercise, while other transcripts showed sustained induction or repression over the 24 hours after exercise. Increases in a number of known transcriptional regulators, including PPAR-α, CERM and CEBPD, were observed 2-hours after exercise. Pathway analysis demonstrated coordinated changes in expression of genes with known functional relationships, including genes involved in muscle remodeling and growth, intermediary metabolism and immune regulation. Conclusion: Sustained endurance exercise by Alaskan sled dogs induces coordinated changes in gene expression with a clear temporal pattern. RNA expression profiling has the potential to identify novel regulatory mechanisms and responses to exercise stimuli.
2009-07-01 | GSE15117 | GEO
Project description:Background: Muscle responses to exercise are complex, and potentially include acute responses to exercise-induced injury as well as longer-term adaptive training responses. Using Alaskan sled dogs as an experimental model, changes in muscle gene expression were analyzed to better understand the temporal changes that occur after severe exercise. Methods: Dogs were randomly assigned to undertake in a 160 km run (n=9), or to remain at rest (n=4). Biceps femoris muscle was obtained by needle biopsy from the unexercised dogs and two dogs at each of 2, 6 and 12 hours after the exercise and from 3 dogs 24 hours after exercise. RNA was extracted and microarray analysis used to define gene transcriptional changes. Results: Nine hundred sixty three transcripts exhibited statistically significant change over time after exercise as compared to the unexercised dogs. The changes in gene expression after exercise occurred in a clear temporal pattern and included transcripts with increased expression 2 hours after exercise with a return towards resting levels by 6 hours after exercise. Other transcripts demonstrated increased expression which peaked at six hours after exercise, while other transcripts showed sustained induction or repression over the 24 hours after exercise. Increases in a number of known transcriptional regulators, including PPAR-α, CERM and CEBPD, were observed 2-hours after exercise. Pathway analysis demonstrated coordinated changes in expression of genes with known functional relationships, including genes involved in muscle remodeling and growth, intermediary metabolism and immune regulation. Conclusion: Sustained endurance exercise by Alaskan sled dogs induces coordinated changes in gene expression with a clear temporal pattern. RNA expression profiling has the potential to identify novel regulatory mechanisms and responses to exercise stimuli. Subjects were 13 Alaskan sled dogs aged 4.5 + 2.5 years (mean + SD) and weighing 23.3 + 2.5 kg. Dogs were randomly assigned to two groups â one group of 9 dogs subsequently ran 160 km in 24 hours as 2 sessions of 80 km, separated by a 6 hour rest period. The second group consisted of four dogs housed in unheated kennels, their usual housing, for the duration of the experiment. All dogs were from the same kennel. Dogs were fed a commercial kibble (Eukanuba, Iams Company, Dayton, OH) supplemented with frozen meat during the 8 weeks preceding the study and throughout the study period. The dogâs diet was consistent before, during and after the exercise bout. All dogs had completed 1590 + 100 km of training runs in the 3 months before the study. The dogs had not exercised for 72 hors before the start of this study. Dogs in the exercise group ran as a team pulling a lightly laden sled and driver over packed snow. Ambient temperatures were -20o to -10o C with no wind. Dogs completed the two 80 km runs in 23 hours, including the 6 hour rest period. Blood samples were collected by jugular venepuncture from all dogs the day before exercise, and within a 10 minute window at 2, 6, 12, and 24 hours after completing the second run. Samples were collected into evacuated glass tubes containing a clot enhancer. Muscle samples were collected from each of two dogs within a 10 minute window at 2, 6 and 12 hours after completing exercise and from three dogs 24 hours after completing exercise. Muscle samples were collected from each of the four unexercised dogs within two hours of the other dogs initiating their exercise bout. Each dog had only one biopsy procedure performed. Muscle samples were collected from the biceps femoris muscle using a needle biopsy that yielded approximately 40-60 mg of muscle. The biopsy was performed after clipping and aseptic preparation of the skin overlying the biopsy site. The dog was anesthetized with propofol (6 mg/kg, IV, maintained as necessary with 2 mg/kg additional boluses), a cuffed orotracheal tube placed and the dog ventilated with a hand-held ventilation bag. When adequate anesthesia had been obtained a 5 mm incision was made in the skin. A sterile biopsy needle (12 g PGI EZ Core, Products group International, Inc. Lyons, CO) was then inserted through the incision and a sample of muscle collected. If necessary, repeated collections of muscle were made until a minimum of 40 mg of muscle has been collected from an individual dog. The skin incision was closed with tissue glue and an antibiotic ointment applied. The dog was monitored closely until recovery from anesthesia was complete. Carprofen (4.4 mg/kg, orally) was administered when the dog had recovered sufficiently from anesthesia to have a gag reflex.
2010-05-16 | E-GEOD-15117 | biostudies-arrayexpress
Project description:Tryptophan (Trp), an indispensable amino acid for dogs, is the precursor of serotonin, a neurotransmitter with a variety of effects throughout the body, including the ability to modulate cardiac and pulmonary activity. This study aimed to investigate the effects of a 12-week incremental exercise regimen and supplemental dietary Trp on heart rate (HR) and respiratory rate (RR) in client-owned sled dogs. Sixteen Siberian huskies were randomly allocated to either treatment or control diet groups. Both groups were fed a control diet (Trp to large neutral amino acid ratio of 0.047:1); however, treatment dogs received a Trp supplement to achieve a Trp to large neutral amino acid ratio of 0.075:1. Every three weeks, external telemetry equipment was used to non-invasively measure and record HR and RR at a resting, working, and post-exercise state in a controlled exercise challenge. A mixed model was used to test differences between diet, activity parameter, and week. Dietary Trp supplementation had no effect on HR or RR. Independent of diet, resting, working, post-exercise HR, and time to recover post-exercise HR decreased from week -1 to week 11 (p < 0.05). Resting HR had the greatest reduction from week -1 to week 11 (21%, p < 0.05). Working RR did not change with exercise (p > 0.10), but rRR and postRR decreased from week -1 to week 11 (p < 0.05). These data suggest that the exercise regimen the dogs were subjected to may have positively impacted the dogs' capacity to sustain aerobic exercise, whereas Trp supplementation had no effect on HR or RR.
| S-EPMC7559096 | biostudies-literature
Project description:Using sled dogs as exercise model, our objectives of this study were to 1) assess the effects of one acute bout of high-intensity exercise on surface GLUT4 concentrations on easily accessible peripheral blood mononuclear cells (PBMC) and 2) compare our findings with published research on exercise induced GLUT4 in skeletal muscle. During the exercise bout, dogs ran 5 miles at approximately 90% of VO2 max. PMBC were collected before exercise (baseline), immediately after exercise and after 24h recovery.GLUT4 was measured via ELISA. Acute exercise resulted in a significant increase on surface GLUT4 content on PBMC. GLUT4 was increased significantly immediately after exercise (~ 50%; p<0.05) and reduced slightly by 24h post-exercise as compared to baseline (~ 22%; p>0.05). An effect of acute exercise on GLUT4 levels translocated to the cell membrane was observed, with GLUT4 levels not yet returned to baseline after 24h post-exercise. In conclusion, the present investigation demonstrated that acute high-intensity exercise increased GLUT4 content at the surface of PBMC of sled dogs as it has been reported in skeletal muscle in other species. Our findings underline the potential use of peripheral blood mononuclear cell GLUT4 protein content as minimally invasive proxy to investigate relationships between insulin sensitivity, insulin resistance, GLUT4 expression and glucose metabolism.
| S-EPMC4554329 | biostudies-literature
Project description:Alaskan sled dogs are a genetically distinct population shaped by generations of selective interbreeding with purebred dogs to create a group of high-performance athletes. As a result of selective breeding strategies, sled dogs present a unique opportunity to employ admixture-mapping techniques to investigate how breed composition and trait selection impact genomic structure. We used admixture mapping to investigate genetic ancestry across the genomes of two classes of sled dogs, sprint and long-distance racers, and combined that with genome-wide association studies (GWAS) to identify regions that correlate with performance-enhancing traits. The sled dog genome is enhanced by differential contributions from four non-admixed breeds (Alaskan Malamute, Siberian Husky, German Shorthaired Pointer, and Borzoi). A principal components analysis (PCA) of 115,000 genome-wide SNPs clearly resolved the sprint and distance populations as distinct genetic groups, with longer blocks of linkage disequilibrium (LD) observed in the distance versus sprint dogs (7.5-10 and 2.5-3.75 kb, respectively). Furthermore, we identified eight regions with the genomic signal from either a selective sweep or an association analysis, corroborated by an excess of ancestry when comparing sprint and distance dogs. A comparison of elite and poor-performing sled dogs identified a single region significantly associated with heat tolerance. Within the region we identified seven SNPs within the myosin heavy chain 9 gene (MYH9) that were significantly associated with heat tolerance in sprint dogs, two of which correspond to conserved promoter and enhancer regions in the human ortholog.
| S-EPMC3320045 | biostudies-literature
Project description:Arctic-Adapted Dogs Emerged at the Pleistocene-Holocene Transition
| PRJNA608847 | ENA
Project description:The Alaskan sled dog offers a rare opportunity to investigate the development of a dog breed based solely on performance, rather than appearance, thus setting the breed apart from most others. Several established breeds, many of which are recognized by the American Kennel Club (AKC), have been introduced into the sled dog population to enhance racing performance. We have used molecular methods to ascertain the constitutive breeds used to develop successful sled dog lines, and in doing so, determined the breed origins of specific performance-related behaviors.One hundred and ninety-nine Alaskan sled dogs were genotyped using 96 microsatellite markers that span the canine genome. These data were compared to that from 141 similarly genotyped purebred dog breeds. Sled dogs were evaluated for breed composition based on a variety of performance phenotypes including speed, endurance and work ethic, and the data stratified based on population structure.We observe that the Alaskan sled dog has a unique molecular signature and that the genetic profile is sufficient for identifying dogs bred for sprint versus distance. When evaluating contributions of existing breeds we find that the Alaskan Malamute and Siberian Husky contributions are associated with enhanced endurance; Pointer and Saluki are associated with enhanced speed and the Anatolian Shepherd demonstrates a positive influence on work ethic.We have established a genetic breed profile for the Alaskan sled dog, identified profile variance between sprint and distance dogs, and established breeds associated with enhanced performance attributes. These data set the stage for mapping studies aimed at finding genes that are associated with athletic attributes integral to the high performing Alaskan sled dog.
| S-EPMC2920855 | biostudies-other
Project description:Although emerging data suggests a greater influence of gluconeogenic precursors, endurance sled dogs have long appeared to rely heavily on fatty acid oxidation for sustained energy production. However, much of the research investigating lipid utilization during exercise in sled dogs has been carried out with dogs subjected to extended bouts of endurance exercise. Less is known about changes in fatty acid composition in endurance training sled dogs subjected to short bouts of exercise, and fewer data define how fatty acid composition may change in distinct lipid fractions. As such, the study objective was to assess whether short bouts of submaximal exercise would affect fatty acid profiles of serum lipid fractions in endurance training sled dogs. Fifteen privately-owned Siberian huskies were used (8 females: 4 intact, 4 spayed; 7 males: 2 intact, 5 neutered), with an average age of 4.6 ± 2.5 years and body weight of 24.8 ± 4.2 kg. Throughout the diet acclimation and remainder of the study, all dogs were fed a dry extruded diet that met or exceeded all AAFCO nutrient recommendations. Dogs were weighed weekly and fed to maintain baseline body weight. A 12-week exercise regimen was designed to incorporate weekly increases in running distance, but weather played a role in setting the daily distance. On weeks 2, 5, and 11, an exercise challenge was implemented whereby dogs would run 4 km at 15 km/h in teams of 4. Pre- and post-exercise blood samples were taken, and gas chromatography was used to evaluate fatty acid profiles of all identified serum lipid fractions (cholesterol ester, diacylglycerol, free fatty acid, phospholipids, triglyceride). Data were analyzed using PROC MIXED of SAS, with dog as a random effect and week and sampling time point as fixed effects. Composition of oleic (18:1n9), linoleic (18:2n6), and alpha-linolenic (18:3n3) acids in the free fatty acid fraction decreased by ~9, 10, and 60%, respectively, following exercise (P ≤ 0.05). The results presented herein suggest that aside from a degree of depletion of these 18-carbon unsaturated fatty acids, short bouts of submaximal exercise do not induce considerable changes to sled dog fatty acid profiles.
| S-EPMC8421022 | biostudies-literature
Project description:BACKGROUND:Noninvasive methods of quantitating exercise tolerance in dogs with neuromuscular disease are needed both for clinical and research use. The 6-minute walk test (6MWT) has been validated as a reliable test of exercise tolerance in dogs with pulmonary and cardiac disease, but not in dogs with neuromuscular disease. HYPOTHESIS/OBJECTIVES:Distance walked and number of steps taken during 6MWT will differ between Labrador retriever dogs with centronuclear myopathy (CNM) and control (ie, healthy) littermates. ANIMALS:Eight purebred Labrador retrievers were drawn from a purpose-bred research colony (status: 3 clear, 2 carrier, and 3 homozygous mutants for the protein tyrosine phosphatase-like A (PTPLA) gene mutation associated with CNM). METHODS:Pilot, prospective, Case-controlled study. Researchers were blinded to disease status. Each dog was leash-trained and acclimatized to the testing area (length, 12.8 m). At the start of testing, each animal was fitted with a pedometer, a timer was started, and dogs were allowed to walk at their own pace for 6 minutes. Distance walked and pedometer readings were recorded. RESULTS:Degree of paresis varied among affected dogs, and was reflected by significant differences in distance walked between CNM-affected dogs and those with clear and carrier genotypes (P = .048). Pedometer readings did not vary according to genotype (P = .86). CONCLUSIONS:The 6MWT appears to differentiate between the ambulatory capacity of normal and CNM-affected dogs. Additional studies are needed to confirm this relationship in a larger number of dogs, and to evaluate the ability of the 6MWT to differentiate between dogs with variable severity of neuromuscular disease-associated exercise intolerance.
| S-EPMC4913584 | biostudies-literature
Project description:BackgroundGreenland sled dogs (GSD) are a unique, genetically isolated population of dogs living under exceptional environmental conditions. Metabolism, and thereby thyroid hormones are affected by multiple factors. Among other activity, energy balance and environmental conditions are important. A breed-specific reference interval (RI) can be useful for diagnostics of potential thyroid-related pathologies. The aim of this study was to establish RIs of the thyroid hormones thyroxin (T4), free thyroxin (fT4), and thyroid stimulating hormone (TSH) in GSD. In addition to evaluate the effect of sex, age, season, management, and body condition score (BCS) in GSD. Physical exams and cephalic venous blood sampling were performed in the period of 2018-2019 from 265 GSD managed either privately or by the Danish navy. Serum biochemical analyses, including C-reactive protein, were performed and RIs were determined for TSH, T4 and fT4 in only healthy dogs. The RIs were determined using American Society for Veterinary Clinical Pathology guidelines and the effect of varying factors were evaluated by linear regression and further tested by Mann-Whitney test.Results144 GSD were included in the reference group resulting in RIs: T4: 6.44-48.65 nmol/L; fT4: 3.91-18.51 pmol/L; and TSH: 0.04-0.55 ng/mL. Female GSD had significantly higher concentrations of T4 (P = 0.039) and fT4 (P = 0.015) compared to males; a positive correlation between TSH and aging was found; T4 concentrations were significantly higher (P = 0.003) during summer; and TSH concentrations were lower in GSD managed by the navy (P < 0.0001). BCS was higher (P < 0.0001) in Sirius GSD compared to civilian GSD, and BCS was positively correlated with T4 and negatively correlated with TSH.ConclusionsReference intervals for T4, fT4 and TSH in GSD were established. The RI for T4 and fT4 was lower compared to other breeds. In addition, sex, age, season, management and BCS demonstrated variable effects on thyroid hormones. Our results can be used as a foundation for improving management and further research of GSD.
| S-EPMC8630915 | biostudies-literature