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Obese mice fed a high-fat diet and given prednisone once a week had improved exercise endurance, became stronger, increased their lean body mass and lost weight, reports a new Northwestern Medicine study. The mice also had increased muscle metabolism.
Prednisone once a week promoted nutrient uptake into the muscles.
Researchers also found that 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 researchers also showed that mice that were already overweight from eating a high-fat diet also had benefits after prednisone once a week, experiencing increased strength, running capacity and lower blood sugar.
“These studies were performed on mice. But if the same routes apply in humans, then prednisone once a week could benefit obesity,” says senior author Dr. Elizabeth McNally, Director of the Center for Genetic Medicine at Northwestern University Feinberg School of Medicine.
McNally is also a Northwestern Medicine physician and 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, where we intermittently ‘pulse’ the animals with prednisone once a week, are strikingly different. Obesity is a big problem, and the idea that prednisone once a week can promote nutrient uptake into the muscles can be an approach to treatment of obesity. “
The study will be published April 1 in the Journal of Experimental Medicine.
Most of what we know about steroids like prednisone comes from studies that look at what happens when prednisone, a glucocorticoid steroid, is taken every day.
“We see a very different result when taken once a week,” McNally said. “We need to fine-tune the dosage to find out the right amount to make this work in humans, but knowing that adiponectin can be a marker can give a hint as to what the right human dose is. is.”
McNally described the weekly dose as “a bolus, or tip, of nutrients that go into your muscle.”
“We think there is something special about promoting this increase in nutrients into muscles at intervals and that it can be an effective way to improve lean body mass,” she added.
“What’s exciting to me about this work is the discovery that a simple change in dosing frequency can transform glucocorticoid drugs from inducers to preventers of obesity,” said the corresponding author Mattia Quattrocelli. “Chronic intake of these drugs once daily is known to promote obesity. Here we show that dosing the same type of drug intermittently – in this case once a week – reverses this effect, promotes muscle metabolism and energy consumption and limits metabolic stress. induced by a high-fat diet. “
Quattrocelli, who started the research while in Northwestern, is now an assistant professor at Cincinnati Children’s Hospital Medical Center and the Department of Pediatrics at the University of Cincinnati.
Can weekly dose still benefit patients with immune disorders?
Many patients take prednisone daily for various immune conditions. Known side effects of daily prednisone include weight gain and even muscle atrophy with weakness. Investigators want to determine if patients can get the same immune benefit with intermittent prednisone dosing, which could be much more beneficial for the muscle.
Research began in muscular dystrophy
In previously published studies, McNally’s team discovered that giving prednisone at intervals was helpful for muscle wasting, and once a week prednisone showed improved strength.
The group also recently reported results from a pilot study in people with muscle wasting, in which a weekly dose of prednisone improved lean mass.
Not one-size-fits-all for prednisone dosing
People have different reactions to prednisone dosage.
McNally wants to determine which biomarkers are most critical for marking that they have 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 adjust the dosage of prednisone,” she said.
The group also recently showed that weekly prednisone uses strikingly different molecular pathways to strengthen the muscle of male versus female mice, based on a new study just published in the Journal of Clinical Investigation by Isabella Salamone, a graduate student at McNally’s laboratory.
The circadian connection
The benefits of weekly prednisone are linked to circadian rhythms, reports another new study from Northwestern and the University of Cincinnati published last month in Science Advances.
Human cortisol and steroid levels rise early in the morning before you wake up.
“If you do not give the drug at the right time of day, you will not get the answer,” Quattrocelli said. “In mice, we achieved good effects with intermittent prednisone in muscle mass and function when we dose them at the beginning of their daytime hours. Mice have a circadian rhythm reversed to us as they generally sleep during the daytime hours and are active at night. This could mean , that the optimal dosing time for humans during the day could be late afternoon / early evening, but this should be tested appropriately. ”
Are stronger, slimmer mice equal to stronger, slimmer people?
The biggest warning is that these studies are performed in mice, McNally said.
“While we are encouraged by the pilot study in people with muscle wasting, mouse muscles have more fast-twitch fibers than humans, and slow-twitch muscles may be different,” McNally said. “More research is needed to try to better understand whether the same mechanisms work in human muscles.”
Steroid treatments for Duchenne muscular dystrophy may depend on the clock More information: Mattia Quattrocelli et al, Intermittent prednisone treatment in mice promotes exercise tolerance in obesity through adiponectin, Journal of Experimental Medicine (2022). DOI: 10.1084 / jem.20211906
Isabella M. Salamone et al., Intermittent glucocorticoid therapy improves skeletal muscle performance through sexually dimorphic mechanisms, Journal of Clinical Investigation (2022). DOI: 10.1172 / JCI149828
Quote: Can weekly prednisone treat obesity? (2022, April 1) Retrieved April 1, 2022 from https://medicalxpress.com/news/2022-04-weekly-prednison-obesity.html
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