Wednesday 26 February 2020

How mitochondria respond to exercise, high fat die


Dubbed the powerhouses of the cell because they turn nutrients into energy, mitochondria are tiny organelles that live inside the cell and are key to metabolic health. New research offers fresh insights into how they work and what keeps them healthy.
Because of the role of the mitochondria in metabolic and overall health, previous research has suggested that dysfunction in these organelles may have implications in conditions such as obesity and diabetes.
Other conditions that mitochondrial dysfunction is involved in include age-related neurodegenerative conditions, such as Parkinson’s, Alzheimer’s, and Huntington’s disease.
In fact, mitochondrial dysfunction may be at the root of the aging process, in general. Although also disputed, the so-called mitochondrial-free radical theory of aging is a popular one, and more than one study has suggested that boosting mitochondria’s health can prevent cells from aging.
But what exactly keeps mitochondria in tip-top shape or makes them “unhealthy” remains unknown.
Previously, researchers thought that one molecular pathway that they called autophagy might offer precious clues to what keeps mitochondria healthy or makes them dysfunctional.
Autophagy — a word derived from ancient Greek to mean “self-eating” — is a “cellular survival pathway that recycles intracellular components to compensate for nutrient depletion and ensures the appropriate degradation of organelles.”
Therefore, it is key for the health of mitochondria, and previous studies have shown that exercise boosts autophagy, and the researchers believed that a high fat diet might impair the process.
The latest research looked at this pathway in mice and examined the ways in which exercise and a high fat diet affect it, as well as how these changes affect mitochondrial health.
Sarah Ehrlicher, a doctoral candidate in the College of Public Health and Human Sciences at Oregon State University in Corvallis, is the first author of the paper, which appears in the FASEB Journal.
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Ehrlicher and colleagues “stressed” the mitochondria of transgenic mice by making the animals exercise on a treadmill. Genetic alterations impaired their exercise-induced autophagy pathway.
The rodents were euthanized 36 hours after their last bout of exercise and 4 hours after their last meal, and the researchers examined the mitochondria in the rodents’ muscle cells.
What the team found was that despite the genetic modification and the added stress of exercise, the mitochondrial function of the mice’s muscles remained intact.
As a next step, Ehrlicher and colleagues fed the mice a high fat diet in addition to the exercise regimen to stress the mitochondria even more.
Again, the mice’s mitochondria showed signs of intact health and adaptation, even with the autophagy pathway blocked. This, explains the study’s lead author, suggests that the mitochondria have alternative ways to stimulate recycling and limit the damage.
Matt Robinson, a researcher in the same department as Ehrlicher and the last and corresponding author of the study, reports on the results.
He says, “[When] these animals were given a high fat diet, they got better at burning off those fats. If they were given just the exercise, they were able to make more mitochondria, which is good from an exercise perspective. And those adaptations seem to be very specific.”
The authors add that the findings elucidate more about how mitochondria work and what keeps them healthy.
The study “helps lay some future groundwork for how we can optimize (muscle and mitochondrial) health to promote their health with diseases like obesity, diabetes, even some implications with aging — conditions that we know have compromised mitochondria,” says Robinson.
Exercise may be one such way of optimizing mitochondrial and metabolic health. “Even without changes in weight, exercise has this amazing ability to improve metabolic health,” Ehrlicher says.
Obese mice do not seem to have an obvious pathway dysfunction in their mitochondria, and the muscles just seem to respond and adapt well to new stress, whether that is exercise or a high fat diet.

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