Page 16 - Abacoa Community News - December '21

Page 16, Abacoa
scieNce oN the cUttiNg edge

The Scripps Research Institute News

Study Reveals Molecular normal, and found that this relatively simple genetic use in the United States because of its adverse side effects,

Pathway By Which Intense juicing of the mice quickly reproduced the strength and which include heart palpitations and muscle tremors.
“This research suggests that exercise that releases

performance benefits of intense exercise, giving them
Exercise Promotes Weight Loss bigger muscles and exercise capacity. these stress hormones, such as with high intensity or
“It was quite amazing,” Nettles says. “Imagine being switching your routine will improve maintenance of
Boosting the activity of one gene in the muscles of able to ride a bike at 10 miles an hour for an hour, and weight loss,” Nettles says.
mice powerfully enhances their ability to lose weight then just a week later being able to ride at 20 miles an hour In addition to Nettles, authors of “Activation of Crtc2/
with fasting. for two hours – that was the degree of the performance Creb1 in skeletal muscle enhances weight loss during
When you try to lose weight by eating less, your body enhancement we saw in these mice.” intermittent fasting” include Nelson Bruno, Jerome
tends to resist by slowing its metabolism and ramping In the new study, the researchers examined CRCT2’s Nwachukwu, Sathish Srinivasan, Richard Hawkins and
up the hunger pangs. This is why diets fail so often. exercise-like impact in the context of dieting. Prior studies Michael Conkright of Scripps Research; David Hughes, and
But people who maintain long-term weight loss almost have shown that exercise is very important for sustaining Sue Bodine of the University of Iowa; David Sturgill and
invariably exercise, and a new study from scientists at weight-loss when dieting. Exercise doesn’t just directly Gordon Hager of the National Cancer Institute; and Stephen
Scripps Research reveals key molecular details of this burn calories. It also, among other effects, raises the Hurst and Shey-Shing Sheu of Thomas Jefferson University.
weight loss-enhancing effect. background calorie-burning rate, countering the metabolic
slowing that normally occurs with lowered food intake. Potential Treatment For ALS,
The scientists found this same “exercise effect” in mice
whose muscles had overactive CRCT2. Over two weeks Frontotemporal Dementia
of an alternate-day fasting regimen, the high-CRCT2 mice
lost twice as much weight as normal-CRCT2 mice while Targets RNA
maintaining a higher rate of metabolism and showing less
binge eating when food was available. The high-CRCT2 Compound co-opts a natural enzyme to degrade a
mice also lost mainly fat, whereas the normal mice lost deadly disease at its source, erasing 70 percent of a
mostly lean mass—which is to say, mostly muscle. toxic protein in mice.
Apart from illuminating these exercise-activated One of the most commonly inherited forms of ALS
pathways, the research also made clear that the stress and frontotemporal dementia (FTD) is referred to as C9
hormone norepinephrine has a more complex role than ALS/FTD, so named for the repeated section of DNA on
has traditionally been assumed. chromosome 9 that causes it.
“We’ve thought of the stress hormones norepinephrine A collaboration led by scientists at Scripps Research in
The researchers, who report their findings in the FASEB and epinephrine (also known as noradrenaline and Florida has successfully treated the genetic disease in mice,
(Federation of American Societies for Experimental adrenaline) as being released during intense or new with a potential drug molecule engineered in the lab of chemist
Biology) Journal, engineered mice to overexpress a gene exercise to help break down fat and other molecules in Matthew Disney, Ph.D. The compound works in a new way,
called CRCT2. This gene is among those activated by the short term for use as fuel,” Nettles says. “We haven’t by directing the cell’s own immune machinery to degrade and
intense or new exertion, and it is known to account for many thought about them as regulators of long-term metabolism eliminate the disease-causing RNA. The team’s study was
of the fitness benefits of high-intensity interval workouts. and muscle-building – so that’s a big change.” published recently in the journal Science Translational Medicine.
The scientists found that by boosting CRCT2 they Developing a drug, for example a future obesity or Collaborators include Leonard Petrucelli, Ph.D., of the Mayo
also could powerfully counter the metabolism-slowing, diabetes drug, that boosts CRCT2 as the researchers did Clinic in Jacksonville, and Jeffrey Rothstein, M.D., Ph.D., of
hunger-boosting effects of fasting in mice, allowing the in this study, is somewhat problematic, Nettles says. An Johns Hopkins University in Baltimore.
animals to lose more weight compared to mice who lacked existing drug that has this effect is considered an illicit
the extra CRCT2 activity. performance-enhancer and is not approved for any human The Scripps Research Institute News on page 18
“Just by manipulating this one gene we were able to
reproduce weight-loss benefits of high intensity interval
training, including the maintenance during fasting of a
higher metabolic rate, greater loss of fat mass, and greater
resistance to the loss of muscle mass,” says study senior
author Kendall Nettles, Ph.D., associate professor in the
Department of Integrative Structural and Computational
Biology at Scripps Research in Florida.
The Benefits Of Stress
Surveys by the U.S. Centers for Disease Control
suggest that about 70 percent of Americans qualify as
overweight or obese, reflecting one of the most striking
and worrisome health trends of modern times. Overweight
and obesity are associated with elevated risks of a long
list of disorders, from diabetes to cardiovascular disease.
Thus there is a particular urgency to the study of the
biology of weight gain and weight loss.
In a 2014 study, Scripps Research investigators
including Nettles detailed how CRCT2 is activated Act Now and Do the
downstream of the surge of the stress hormone
norepinephrine, which occurs when intense exercise Holiday Hustle Bustle with
triggers the “fight or flight” stress response. The Your New Match!
researchers engineered mice in which they could switch
on CRCT2 activity in muscles at much higher levels than

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