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      Neither autophagy nor exercise training mode affect exercise-induced beneficial adaptations in high fat-fed mice

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          Abstract

          Exercise mitigates obesity-associated pathologies; however, there is controversy regarding optimal exercise interventions. Autophagy, is known to decrease during obesity and is an important moderator for exercise adaptations.

          Purpose

          To investigate individual and combined effects of different exercise interventions and autophagy inhibition on exercise adaptations during obesity.

          Methods

          C57BL/6J mice initiated 45% high fat diet at 8 weeks of age. After 6 weeks of diet, animals were divided into moderate (MOD) or high intensity interval training interventions (HIIT), animals were further divided into autophagy inhibition or vehicle conditions (n = 10/group). Animals exercised and autophagy was inhibited 3X/week by NSC185058 injections, thereby blocking autophagosome formation. Interventions continued for 4 weeks.

          Results

          High fat diet impaired glucose handling ∼17%; exercise interventions normalized glucoregulation to pre-high fat diet levels, without differences between any interventions. High fat diet induced ∼25% decrease in aerobic capacity, which returned to baseline after exercise interventions, with no differences between any interventions. No effects of autophagy inhibition were noted.

          Conclusions

          HIIT and MOD training confer similar health-related adaptations.

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          Most cited references43

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          Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).

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            Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis.

            Exercise has beneficial effects on human health, including protection against metabolic disorders such as diabetes. However, the cellular mechanisms underlying these effects are incompletely understood. The lysosomal degradation pathway, autophagy, is an intracellular recycling system that functions during basal conditions in organelle and protein quality control. During stress, increased levels of autophagy permit cells to adapt to changing nutritional and energy demands through protein catabolism. Moreover, in animal models, autophagy protects against diseases such as cancer, neurodegenerative disorders, infections, inflammatory diseases, ageing and insulin resistance. Here we show that acute exercise induces autophagy in skeletal and cardiac muscle of fed mice. To investigate the role of exercise-mediated autophagy in vivo, we generated mutant mice that show normal levels of basal autophagy but are deficient in stimulus (exercise- or starvation)-induced autophagy. These mice (termed BCL2 AAA mice) contain knock-in mutations in BCL2 phosphorylation sites (Thr69Ala, Ser70Ala and Ser84Ala) that prevent stimulus-induced disruption of the BCL2-beclin-1 complex and autophagy activation. BCL2 AAA mice show decreased endurance and altered glucose metabolism during acute exercise, as well as impaired chronic exercise-mediated protection against high-fat-diet-induced glucose intolerance. Thus, exercise induces autophagy, BCL2 is a crucial regulator of exercise- (and starvation)-induced autophagy in vivo, and autophagy induction may contribute to the beneficial metabolic effects of exercise.
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              Trends in Obesity Among Adults in the United States, 2005 to 2014.

              Between 1980 and 2000, the prevalence of obesity increased significantly among adult men and women in the United States; further significant increases were observed through 2003-2004 for men but not women. Subsequent comparisons of data from 2003-2004 with data through 2011-2012 showed no significant increases for men or women.
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                Author and article information

                Contributors
                Journal
                Sports Med Health Sci
                Sports Med Health Sci
                Sports Medicine and Health Science
                Chengdu Sport University
                2666-3376
                09 March 2020
                March 2020
                09 March 2020
                : 2
                : 1
                : 44-53
                Affiliations
                [a ]Integrative Muscle Metabolism Laboratory, Exercise Science Research Center, Department of Human Health Performance and Recreation, University of Arkansas, USA
                [b ]Exercise Muscle Biology Laboratory, Exercise Science Research Center, Department of Human Health Performance and Recreation, University of Arkansas, USA
                Author notes
                []Corresponding author. HPER 321, University of Arkansas, 155 Stadium Dr. Fayetteville, AR, 72701, USA. npgreene@ 123456uark.edu
                Article
                S2666-3376(20)30007-X
                10.1016/j.smhs.2020.03.003
                9219353
                35783331
                d1bc5249-d509-46c7-a851-cbf61d892c3e
                © 2020 Chengdu Sport University. Production and hosting by Elsevier B.V. on behalf of KeAi.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 6 November 2019
                : 28 February 2020
                : 4 March 2020
                Categories
                Research Article

                insulin resistance,exercise capacity,glucose tolerance,obesity

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