scholarly journals Acylcarnitine profile in Alaskan sled dogs during submaximal multiday exercise points out metabolic flexibility and liver role in energy metabolism

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256009
Author(s):  
Irene Tosi ◽  
Tatiana Art ◽  
François Boemer ◽  
Dominique-Marie Votion ◽  
Michael S. Davis

Alaskan sled dogs develop a particular metabolic strategy during multiday submaximal exercise, allowing them to switch from intra-muscular to extra-muscular energy substrates thus postponing fatigue. Specifically, a progressively increasing stimulus for hepatic glycogenolysis and gluconeogenesis provides glucose for both fueling exercise and replenishing the depleted muscle glycogen. Moreover, recent studies have shown that with continuation of exercise sled dogs increase their insulin-sensitivity and their capacity to transport and oxidize glucose and carbohydrates rather than oxidizing fatty acids. Carnitine and acylcarnitines (AC) play an essential role as metabolic regulators in both fat and glucose metabolism; they serve as biomarkers in different species in both physiologic and pathologic conditions. We assessed the effect of multiday exercise in conditioned sled dogs on plasma short (SC), medium (MC) and long (LC) chain AC by tandem mass spectrometry (MS/MS). Our results show chain-specific modification of AC profiles during the exercise challenge: LCACs maintained a steady increase throughout exercise, some SCACs increased during the last phase of exercise and acetylcarnitine (C2) initially increased before decreasing during the later phase of exercise. We speculated that SCACs kinetics could reflect an increased protein catabolism and C2 pattern could reflect its hepatic uptake for energy-generating purposes to sustain gluconeogenesis. LCACs may be exported by muscle to avoid their accumulation to preserve glucose oxidation and insulin-sensitivity or they could be distributed by liver as energy substrates. These findings, although representing a “snapshot” of blood as a crossing point between different organs, shed further light on sled dogs metabolism that is liver-centric and more carbohydrate-dependent than fat-dependent and during prolonged submaximal exercise.

2014 ◽  
Vol 10 (3) ◽  
pp. 167-172 ◽  
Author(s):  
S.E. Pratt-Phillips ◽  
R.J. Geor ◽  
M. Buser ◽  
A. Zirkle ◽  
A. Moore ◽  
...  

Two experiments were designed to investigate the role of exercise on insulin sensitivity (IS) in Alaskan racing sled dogs. In both experiments, IS was quantified with an isoglycemic-hyperinsulinemic clamp (IHC), whereby IS was defined as the glucose infusion rate (GIR) divided by the mean insulin concentration during the clamp. In Experiment 1, IS was quantified in 12 racing sled dogs during three stages of exercise training: unexercised for 4 months over the summer (deconditioned), and after two and four months of exercise conditioning. At each stage IS was assessed in unexercised dogs (n=6) and 60 h following a standard exercise challenge (n=6) consisting of a 35.4 km run completed in 2.5 h. In Experiment 2, IS was assessed in deconditioned dogs (n=6) and in well-conditioned dogs that had either completed a 708 km race 5-days prior (n=3) or were unraced for the previous month (n=3). In Experiment 1, there were no significant differences (Pã0.05) in GIR or IS between the three levels of conditioning, nor were there any effects of the exercise bout 60 h prior to the IHC. In Experiment 2 there was no significant difference in IS between well-conditioned dogs and untrained dogs (Pã0.05). However, dogs that completed a 708 km race 5-days prior to the IHC had a significantly higher IS than dogs that were deconditioned and those that were conditioned but unraced. These results suggest that the workload of an exercise challenge is a factor in post-exercise changes in IS but that exercise conditioning has little impact on IS in Alaskan sled dogs.


2002 ◽  
Vol 12 (4) ◽  
pp. 398-413 ◽  
Author(s):  
Roy L.P.G. Jentjens ◽  
Asker E. Jeukendrup

Pre-exercise carbohydrate feeding may result in rebound hypoglycemia in some but not all athletes. The aim of the present study was to examine whether insulin sensitivity in athletes who develop rebound hypoglycemia is higher compared with those who do not show rebound hypoglycemia. Twenty trained athletes (V̇O2max of 61.8 ± 1.4 ml · kg−1 · min−1) performed an exercise trial on a cycle ergometer. Forty-five minutes before the start of exercise, subjects consumed 500 ml of a beverage containing 75 g of glucose. The exercise trial consisted of · 20 min of submaximal exercise at 74 ± 1% V̇O2max immediately followed by a time trial. Based upon the plasma glucose nadir reached during submaximal exercise, subjects were assigned to a Hypo group (<3.5 mmol/L) and a Non-hypo group (≥3.5 mmol/L). An oral glucose tolerance test was performed to obtain an index of insulin sensitivity (ISI). The plasma glucose nadir during submaximal exercise was significantly lower (p < .01) in the Hypo-group (n = 10) compared with the Non-hypo group (n = 10) (2.7 ± 0.1 vs. 4.1 ± 0.2 mmol/L, respectively). No difference was found in ISI between the Hypo and the Non-hypo group (3.7 ± 0.4 vs. 3.8 ± 0.5, respectively). The present results suggest that insulin sensitivity does not play an important role in the occurrence of rebound hypoglycemia.


2020 ◽  
Vol 16 (3) ◽  
pp. 197-205
Author(s):  
M.S. Davis ◽  
K.W. Hinchcliff ◽  
K.K. Williamson ◽  
E.C. McKenzie ◽  
C.M. Royer

Prolonged submaximal exercise relies on the steady delivery of oxidizable substrates to the working muscle, with the sources of those substrates either stored reserves or food absorbed from the gastrointestinal tract during exercise. Fat oxidation could be advantageous for this type of exercise because of potentially greater reserves, but recent studies suggest that athletic dogs remain highly dependent on carbohydrate to fuel exercise despite ingesting a high fat diet. The purpose of this study was to characterise the pattern of exercise-induced hormone and substrate concentrations as they relate to carbohydrate and fat metabolism during prolonged submaximal exercise in dogs. Two studies (a 10-dog pilot study and a subsequent primary study using 54 Alaskan sled dogs) were conducted with the dogs running 160 km/day for 4 or 5 days. Blood samples were obtained within 60 min of cessation of daily exercise and in the second study within 30 min of the start of the next day of exercise. Samples were analysed for key hormones and substrates. Results demonstrated the development of a strong hormonal stimulus for glycogenolysis/gluconeogenesis that coincided with sparing and replenishment of muscle glycogen. The stimulus for glycogenolysis/gluconeogenesis tended to diminish during rest periods in the early stages of the exercise challenge, but remained increased during later rest periods and for several days after the conclusion of exercise. These data support the hypothesis that in the face of a high-fat diet, ultra-endurance racing sled dogs rely on large amounts of hepatic glucose output to support prolonged submaximal exercise.


2020 ◽  
Author(s):  
Michael J. Ormsby ◽  
Heather Hulme ◽  
Victor H. Villar ◽  
Gregory Hamm ◽  
Giovanny Rodriguez-Blanco ◽  
...  

AbstractDiabetes is a global health problem that was estimated to be the 7th leading cause of death worldwide in 2016. Type 2 diabetes mellitus (T2DM) is classically associated with genetic and environmental factors, however recent studies have demonstrated that the gut microbiome, which is altered in T2DM patients, is also likely to play a significant role in disease development. Despite this, the identity of microbiome-derived metabolites that influence T2DM onset and/or progression remain elusive. Here we demonstrate that a serum biomarker for T2DM, previously of unknown structure and origin, is actually two microbiome-derived metabolites, 3-methyl-4-(trimethylammonio)butanoate (3M-4-TMAB) and 4-(trimethylammonio)pentanoate (4-TMAP). These metabolites are produced by the Lachnospiraceae family of bacteria, which are highly prevalent in the gut microbiome of T2DM patients and are associated with high dietary fat intake. Treatment of human liver cells with 3M-4-TMAB and 4-TMAP results in a distinct change in the acylcarnitine profile in these cells and significantly reduced their insulin sensitivity; both indicators of T2DM. These results provide evidence of a mechanistic link between gut microbiome derived metabolites and T2DM.


2015 ◽  
Vol 118 (12) ◽  
pp. 1502-1509 ◽  
Author(s):  
Benjamin F. Miller ◽  
Joshua C. Drake ◽  
Frederick F. Peelor ◽  
Laurie M. Biela ◽  
Raymond Geor ◽  
...  

The Alaskan Husky has been specifically bred for endurance performance and is capable of extreme endurance performance. We examined sled dogs in the trained state at the beginning of the race season and after a 1,600-km race (Iditarod). Our hypothesis was that lipids would be the predominant substrate during submaximal exercise in long-distance racing sled dogs, and a 1,600-km race would increase the reliance on lipids during an exercise bout at the same absolute exercise intensity. The experiments were completed over three testing periods, which were completed in January of two different years before participation in a 1,600-km race, or in March shortly after completion of a 1,600-km race. After determination of H13CO3− recovery, the dogs were tested with primed continuous infusions of [1,1,2,3,3-2H]glycerol, [3-13C]lactate, or [6,6-2H2]glucose. During exercise, respiratory exchange ratio was significantly higher in raced (0.92 ± 0.01) compared with nonraced (0.87 ± 0.01) dogs. During exercise, glucose rate of appearance was potentially sustained by a large glycerol rate of disappearance with an increase in lactate rates of oxidation after a 1,600-km race. Therefore, contrary to our hypothesis, the sled dogs were dependent on carbohydrate energy sources, a reliance that increased further after participation in a 1,600-km race.


Author(s):  
Michael S Davis

Abstract The total energy expenditure of a racing sled dog can exceed 500 kcal/kg bodyweight during typical events spanning a week or more. Based on early research, as well as practical considerations, modern commercial diets are formulated to meet these energy requirements using fat and protein. However, more recent research provides a clear picture of a canine athlete with glucocentric metabolism, including many conditioning-induced adaptations oriented towards sustaining submaximal exercise with glucose as the primary metabolic fuel despite the consumption of fat as the primary dietary energy source. The specific strategies used by racing sled dogs to maintain a robust supply of glucose during exercise, as well as the possible role of fat in facilitating that metabolic priority, is the subject of ongoing research.


2021 ◽  
Vol 8 ◽  
Author(s):  
James R. Templeman ◽  
Luciano Trevizan ◽  
David W. L. Ma ◽  
Anna K. Shoveller

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.


Author(s):  
José G. Centeno

Abstract The steady increase in linguistic and cultural diversity in the country, including the number of bilingual speakers, has been predicted to continue. Minorities are expected to be the majority by 2042. Strokes, the third leading cause of death and the leading cause of long-term disability in the U.S., are quite prevalent in racial and ethnic minorities, so population estimates underscore the imperative need to develop valid clinical procedures to serve the predicted increase in linguistically and culturally diverse bilingual adults with aphasia in post-stroke rehabilitation. Bilingualism is a complex phenomenon that interconnects culture, cognition, and language; thus, as aphasia is a social phenomenon, treatment of bilingual aphasic persons would benefit from conceptual frameworks that exploit the culture-cognition-language interaction in ways that maximize both linguistic and communicative improvement leading to social re-adaptation. This paper discusses a multidisciplinary evidence-based approach to develop ecologically-valid treatment strategies for bilingual aphasic individuals. Content aims to spark practitioners' interest to explore conceptually broad intervention strategies beyond strictly linguistic domains that would facilitate linguistic gains, communicative interactions, and social functioning. This paper largely emphasizes Spanish-English individuals in the United States. Practitioners, however, are advised to adapt the proposed principles to the unique backgrounds of other bilingual aphasic clients.


1968 ◽  
Vol 11 (4) ◽  
pp. 767-776 ◽  
Author(s):  
B. Don Franks ◽  
Elizabeth B. Franks

Eight college students enrolled in group therapy for stuttering were divided into two equal groups for 20 weeks. The training group supplemented therapy with endurance running and calisthenics three days per week. The subjects were tested prior to and at the conclusion of the training on a battery of stuttering tests and cardiovascular measures taken at rest, after stuttering, and after submaximal exercise. There were no significant differences (0.05 level) prior to training. At the conclusion of training, the training group was significandy better in cardiovascular response to exercise and stuttering. Although physical training did not significantly aid the reduction of stuttering as measured in this study, training did cause an increased ability to adapt physiologically to physical stress and to the stress of stuttering.


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