Thursday, January 26, 2012

Cellular 'self eating' accounts for some beneficial effects of exercise.

Population studies suggest that exercise protects against diabetes, cancer, and age related diseases such as Alzheimer's. Work by Congcong He et al. has now shown that at least part of this effect is due to the increased "self-eating" (Autophagy) that cells must do to meet the energy demands of exercise. Autophagy recycles used or flawed membranes and internal cell structures by encircling its target material and then dumping it into a compartment that digests it. It has been shown in animal models to reduce diabetes, cancer, and neuro-degenerative diseases. The He et al. work documents that exercise induces autophagy in the skeletal muscles of mice, which in turn lowers glucose and insulin in the bloodstream. Mutant mice that don't induce more autophagy during exercise didn't show this effect. Further, the exercise induced reversal of diabetes induced by overfeeding mice was observed only the mice who showed a exercise induced increased autophagy. Here is the abstract with more details:
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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