Can weekly prednisone treat obesity?

Young man weight loss before after concept

Obese mice gain muscle mass and lose fat with prednisone once a week.

  • Daily prednisone promotes obesity, but weekly prednisone has “strikingly different” results
  • Weekly prednisone promotes nutrient absorption into muscles and improves lean body mass
  • Many people take prednisone daily for immune disorders, leading to weight gain and the development of diabetes-like side effects

Obese mice fed a high-fat diet and given prednisone once a week had improved exercise endurance, grew stronger, increased their lean body mass and lost weight, reports a new study from Northwestern Medicine published in The Journal of Experimental Medicine.

The prednisone administered once a week promoted the absorption of nutrients into the muscles, and the mice also had an increased muscle metabolism.

The researchers also found that these mice had elevated levels of adiponectin, a fat-derived hormone that appears to play an important role in protecting against diabetes and insulin resistance.

The scientists also showed that mice already obese from a high-fat diet benefited from once-weekly dosing with prednisone, as they had increased strength, ability to run and lower blood sugar.

“These studies were conducted on mice. However, if the same pathways are true in humans, then once-weekly prednisone could benefit obesity,” said senior author Elizabeth McNally, MD, PhD, the Elizabeth J. Ward Professor of Genetic Medicine and director of the Center for Genetic Medicine.

McNally is also a physician of Northwestern Medicine and Professor of Medicine in the Department of Cardiology and Biochemistry and Molecular Genetics.

Elizabeth McNally

Senior Author Elizabeth McNally, MD, PhD, Elizabeth J. Ward Professor of Genetic Medicine and Director of the Center for Genetic Medicine. Photo credit: Northwestern University

“Daily prednisone is known to promote obesity and even metabolic syndrome — a disorder involving elevated blood lipids and blood sugar and weight gain,” McNally said. “So these results where we ‘pulse’ the animals intermittently with prednisone once a week are strikingly different. Obesity is a big problem, and the idea that once-weekly prednisone could boost nutrient uptake into muscles could be an approach to treating obesity.”

Most of what we know about steroids like prednisone comes from studies looking at what happens when prednisone, a glucocorticoid steroid, is taken on a daily basis.

“We see a very different result when it’s taken once a week,” McNally said. “We need to fine-tune the dosing to find the right amount for this to work in humans, but knowing that adiponectin could be a marker could provide a clue as to what the right dose is for humans.”

McNally described the weekly dose as “a bolus or spike of nutrients hitting your muscle.”

“We believe that there is something special about delivering this nutrient spike into muscle intermittently and that it can be an efficient way to improve lean body mass,” she added.

“What excites me about this work is the finding that a simple change in dosing frequency can convert glucocorticoid drugs from inducers to preventers of obesity,” said corresponding author Mattia Quattrocelli, PhD. “Chronic once-daily use of these drugs is known to promote obesity. Here we show that intermittent dosing of the same type of drug—in this case, once a week—reverses this effect, boosting muscle metabolism and energy expenditure, and limiting the metabolic stress induced by a high-fat diet.”

Quattrocelli, who initiated the research while at Northwestern, is now an assistant professor at the Cincinnati Children’s Hospital Medical Center and the Department of Pediatrics at the University of Cincinnati.

Can the weekly dose still benefit patients with immune disorders?

Many patients take prednisone daily for various immune disorders. Known side effects of daily prednisone include weight gain and even muscle atrophy with weakness. Researchers want to determine if patients on intermittent prednisone dosing can achieve the same immune benefit, which could be much more beneficial to muscle.

Research started with muscular dystrophy

In previously published research, McNally’s team discovered that intermittent prednisone was helpful for muscular dystrophy and showed that once-weekly prednisone improved strength.

The group also recently reported results from a pilot study in people with muscular dystrophy in which a weekly dose of prednisone improved lean mass.

There is no one-size-fits-all for prednisone dosing

People react differently to prednisone dosage.

McNally wants to determine which biomarkers are most important to mark a positive response to prednisone.

“If we can determine how to select the right prednisone dose that minimizes atrophy factors and maximizes positive markers like adiponectin, then we can truly personalize prednisone dosing,” she said.

The group also recently showed that weekly prednisone uses strikingly different molecular pathways to strengthen muscle in male and female mice, based on a new study just published in 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, according to another new study from Northwestern and the University of Cincinnati published last month scientific advances.

Human cortisol and steroid levels rise 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 a response,” Quattrocelli said. “In mice, we got good effects on muscle mass and function with intermittent prednisone when dosed at the beginning of their day. Mice have an inverse circadian rhythm to ours, as they typically sleep during the day and are active at night. This could mean that the optimal dosing time for humans could be late afternoon/early evening during the day, but this needs to be tested accordingly.”

Do Stronger, Leaner Mice Equal Stronger, Leaner Humans?

The biggest 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 muscles may be different,” McNally said. “Further studies are needed to better understand whether the same mechanisms work in human muscles.”

Reference: “Intermittent Prednisone Treatment in Mice Promotes Exercise Tolerance in Obesity Through Adiponectin” by Mattia Quattrocelli, Michelle Wintzinger, Karen Miz, Manoj Panta, Ashok D. Prabakaran, Grant D. Barish, Navdeep S. Chandel and Elizabeth M. McNally, 1 April 2022, The Journal of Experimental Medicine.
DOI: 10.1084/jem.20211906

The study was funded by National Institutes of Health grants DK121875, HL158531, AG049665, AR052646, and HL061322 and the CCHMC Heart Institute Translational Grant. Can weekly prednisone treat obesity?

Russell Falcon

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