Can weekly prednisone treat obesity?
Obese mice gain muscle mass and lose fat with once weekly prednisone
Date:
April 1, 2022
Source:
Northwestern University
Summary:
Obese mice that were fed a high-fat diet and that received
prednisone one time per week had improved exercise endurance, got
stronger, increased their lean body mass and lost weight, reports
a new study. The mice also had increased muscle metabolism. The
once-weekly prednisone promoted nutrient uptake into the muscles.
FULL STORY ========================================================================== Obese mice that were fed a high-fat diet and that received prednisone one
time per week had improved exercise endurance, got stronger, increased
their lean body mass and lost weight, reports a new Northwestern Medicine study. The mice also had increased muscle metabolism.
==========================================================================
The once-weekly prednisone promoted nutrient uptake into the muscles.
Investigators also found these mice had increased adiponectin levels, a
fat- derived hormone that appears to play an important role in protecting against diabetes and insulin resistance.
The scientists also showed mice that were already obese from eating a
high-fat diet also had benefit after once-weekly prednisone, experiencing increased strength, running capacity and lower blood glucose.
"These studies were done in mice. However, if these same pathways hold
true in humans, then once-weekly prednisone could benefit obesity,"
said senior author Dr. Elizabeth McNally, director of the Center for
Genetic Medicine at Northwestern University Feinberg School of Medicine.
McNally also is a Northwestern Medicine physician and the Elizabeth
J. Ward Professor of Genetic Medicine.
========================================================================== "Daily prednisone is known to promote obesity and even metabolic syndrome
-- a disorder with elevated blood lipids and blood sugar and weight gain," McNally said. "So, these results, in which we intermittently 'pulse' the animals with once-weekly prednisone, are strikingly different. Obesity is
a major problem, and the idea that once-weekly prednisone could promote nutrient uptake into muscle might be an approach to treating obesity."
The study will be published April 1 in the Journal of Experimental
Medicine.
Most of what we know about steroids like prednisone come from studies
looking at what happens when prednisone, a glucocorticoid steroid,
is taken every day.
"We see a very different outcome when it is taken once a week,"
McNally said.
"We need to fine tune dosing to figure out the right amount to make
this work in humans, but knowing adiponectin might be one marker
could provide a hint at determining what the right human dose is."
McNally described the weekly dose as "a bolus, or spike, of nutrients
going into your muscle." "We think there is something special about
promoting this spike of nutrients into muscle intermittently, and that
it may be an efficient way to improve lean body mass," she added.
========================================================================== "What is exciting to me about this work is the finding that a simple
change in the dosing frequency can transform glucocorticoid drugs
from inducers to preventers of obesity," said corresponding author
Mattia Quattrocelli. "Chronic once-daily intake of these drugs is
known to promote obesity. Here we show that dosing the same type of
drug intermittently -- in this case, once weekly - - reverses this
effect, promotes muscle metabolism and energy expenditure, and curtails
the metabolic stress induced by a fat-rich diet." Quattrocelli, who
initiated the research while at Northwestern, is now assistant professor
at Cincinnati Children's Hospital Medical Center and department of
pediatrics at the University of Cincinnati.
Can weekly dose still benefit patients with immune conditions? Many
patients take prednisone daily for different immune conditions. Known
side effects of daily prednisone include weight gain and even muscle
atrophy with weakness. Investigators want to determine whether patients
can get the same immune benefit with intermittent prednisone dosing,
which could be much more beneficial to the muscle.
Research began in muscular dystrophy In previously published research, McNally's team discovered giving prednisone intermittently was helpful
for muscular dystrophy, showing once weekly prednisone improved strength.
The group also recently reported findings from a pilot trial in humans
with muscular dystrophy in which one weekly dose of prednisone improved
lean mass.
Not one-size-fits-all for prednisone dosing People have different
responses to prednisone dosing.
McNally wants to determine which biomarkers are most critical to mark
having a beneficial response to prednisone.
"If we can determine how to choose the right dose of prednisone that
minimizes atrophy factors and maximizes positive markers like adiponectin,
then we can really personalize the dosing of prednisone," she said.
The group also recently showed that weekly prednisone uses strikingly
different molecular pathways to strengthening the muscle in male versus
female mice, based on a new study just published in the Journal of
Clinical Investigation by Isabella Salamone, a graduate student in
McNally's lab.
The circadian connection The benefits of weekly prednisone are linked
to circadian rhythms, reports another new study from Northwestern and University of Cincinnati published last month in Science Advances.
Human cortisol and steroid levels spike early in the morning before you
wake up.
"If you don't give the drug at the right time of day, you don't get the response," Quattrocelli said. "In mice, we obtained good effects with intermittent prednisone in muscle mass and function when we dose them at
the beginning of their daytime. Mice have a circadian rhythm inverted
to us, as they generally sleep during the daytime and are active at
night. This could mean that the optimal dosing time for humans during
the day could be in the late afternoon/early evening, but this needs
to be appropriately tested." Do stronger, leaner mice equal stronger,
leaner humans? The major caveat is that these studies are conducted in
mice, McNally said.
"While we are encouraged by the pilot study in humans with muscular
dystrophy, mouse muscles have more fast-twitch fibers than humans, and slow-twitch muscle could be different," McNally said. "More studies are
needed to try to better understand whether these same mechanisms work in
human muscles." The study was funded by National Institutes of Health
grants DK121875, HL158531, AG049665, AR052646 and HL061322 and the CCHMC
Heart Institute Translational Grant.
========================================================================== Story Source: Materials provided by Northwestern_University. Original
written by Marla Paul.
Note: Content may be edited for style and length.
========================================================================== Journal Reference:
1. Mattia Quattrocelli, Michelle Wintzinger, Karen Miz, Manoj Panta,
Ashok
D. Prabakaran, Grant D. Barish, Navdeep S. Chandel, Elizabeth
M. McNally.
Intermittent prednisone treatment in mice promotes exercise
tolerance in obesity through adiponectin. Journal of Experimental
Medicine, 2022 DOI: 10.1084/jem.20211906 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/04/220401122235.htm
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