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23-01-2012 | Internal medicine | Article

Exercise promotes ‘intracellular recycling’

Abstract

Free abstract

MedWire News: Upregulation of the "intracellular recycling" system, autophagy, is at least partly responsible for the beneficial effects of exercise on glucose and lipid metabolism, US researchers report in Nature.

Autophagy is a system for the breakdown of intracellular components, which functions under normal conditions and is upregulated by starvation. The current study, by Beth Levine (University of Texas Southwestern Medical Center, Dallas) and team, shows that exercise also upregulates autophagy in mice.

The number of autophagosomes in the skeletal and cardiac muscle of the mice increased after about 30 minutes of treadmill running, leveling off after about 80 minutes. Increased autophagy also occurred in tissues involved in glucose and energy homeostasis, the researchers report. These included the liver, pancreas, and adipose tissue.

Levine et al found that exercise-induced autophagy involved breakdown of a complex of the proteins BCL2 and beclin-1, which is also known to be required for autophagy under basal conditions. The team generated mice with a mutated version of BCL2, which allowed autophagy under basal conditions but prevented its occurrence in response to exercise or 48 hours of starvation.

Mice with mutated BCL2 had a lower maximal exercise capacity than wild-type mice, despite generating similar levels of serum lactate and having similar baseline muscle strength and cardiac function.

However, exercise induced significantly smaller reductions in plasma glucose and insulin levels in the BCL2 mutants than the wild-type mice, indicating that the mutated BCL2 impaired the ability of exercise to increase insulin sensitivity. The team observed similar effects in mice deficient in beclin-1.

Eating a high-fat diet for 4 weeks caused weight gain in both wild-type and BCL2 mutant mice, and caused "modest" suppression of basal levels of autophagy in cardiac and skeletal muscle. During an additional 8 weeks of the high-fat diet, mice that did 50 minutes of daily treadmill exercise put on less weight than control mice that did not exercise and this effect was not impacted by BCL2 status.

But mutated BCL2 did affect the beneficial effects of exercise on glucose tolerance. The high-fat diet impaired glucose tolerance in wild-type and BCL2 mutant mice; but whereas the addition of daily exercise markedly improved glucose tolerance in wild-type mice on the high-fat diet, it had no such effect in the BCL2 mutant mice.

Other beneficial effects of exercise on metabolism were also impaired in the BCL2 mutant mice, which had smaller exercise-induced reductions in serum leptin, triglycerides, and cholesterol, relative to wild-type mice, and smaller increases in adiponectin.

"We propose that BCL2-regulated autophagy activation contributes to the beneficial metabolic effects of exercise, and that manipulation of the autophagy pathway and/or the function of the autophagy inhibitory BCL2 protein may be a logical strategy to mimic the health effects of exercise and to prevent or treat impaired glucose metabolism," conclude Levine et al.

"More broadly, on the basis of this newly discovered link between exercise, autophagy and altered metabolism, we speculate that autophagy may represent a cellular mechanism by which exercise prolongs life and protects against cancer, cardiovascular disorders and inflammatory diseases."

By Eleanor McDermid

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