Exercise–induced BCL2–regulated autophagy is required for muscle glucose homeostasis

By Congcong He, Michael C. Bassik, V. Moresi, K. Sun, Yongjie Wei, Z. Zou, Zhenyi An, Joy Loh, J. Fisher, Qihua Sun and 10 more. Nature, 2012

1,102 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/453fc23d88389e5052c3825dade092b9c0105ac7

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Citations in the corpus

Cell Death Signaling. (2015, background): “This process is essential for regulation of exercise-induced autophagy and glucose metabolism in muscles (He et al. 2012).”
Acetyl coenzyme A: a central metabolite and second messenger. (2015, background): “training (He et al., 2012) may be ultimately linked to decreased mitochondrial protein acetylation levels, as it is the case for rats selectively bred for a high running capacity (Overmyer”
Cellular and molecular mechanisms of muscle atrophy (2013, positive): “However, TNFα and pro-inflammatory cytokines also cause insulin resistance and suppression of the IGF1-Akt pathway (de Alvaro et al., 2004; Dogra et al., 2007; Hirosumi et al., 2002).”
Autophagy-Independent Functions of the Autophagy Machinery (2019, background): “Thus, it has become clear that autophagy occupies a central position in the biology of most eukaryotes, interfacing with the regulation of core metabolism (He et al., 2012; Sousa et al., 2016) , damage control (Ferná ndez et al., 2018; Khaminets et al., 2015; Mathew et al., 2007) , and cell death Wa”
Mechanisms of insulin resistance in obesity (2013, background): “Autophagy was reported to mediate exercise signal to improve insulin sensitivity in muscle [120].”