A new study finds that obese mice consuming a high-fat diet and prednisone tablets once a week had improved exercise endurance, increased strength, increased lean body mass, and lost weight.
Prednisone tablets are part of a group of drugs called corticosteroids. It is often administered to treat a variety of diseases such as lupus, asthma, and certain types of arthritis. Yet, a new study by Northwestern University has discovered new usage for prednisone tablets in the form of weight loss.
“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 Centre for Genetic Medicine at Northwestern University, Feinberg School of 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 was published in the Journal of Experimental Medicine.
The effects of prednisone tablets
Prednisone tablets typically are taken daily, however, this study challenged the effects of the medication taken once a week.
“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.”
Many patients take prednisone tablets 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.
Improving muscular strength
In previously published research, McNally’s team discovered that giving prednisone tablets intermittently was helpful for muscular dystrophy, showing that once-weekly prednisone improved strength. The researchers recently reported findings from a pilot trial in humans with muscular dystrophy in which one weekly dose of prednisone improved lean mass.
Furthermore, the researchers intend to determine which biomarkers are most critical to mark having a beneficial response to prednisone tablets. Scientists revealed that weekly prednisone utilised strikingly different molecular pathways to strengthen the muscle in male versus female mice, based on a new study just published in the Journal Clinical Investigation by Isabella Salamone, a graduate student in McNally’s lab.
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 spike early in the morning before you wake up.”If you don’t give the drug at the right time of day, you do not get the response,” Quattrocelli concluded. “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.”