Drug increases brown fat activity in healthy women

Human brown adipose tissue, or brown fat.Journal of Clinical Investigation

What

A National Institutes of Health study found that chronic treatment with mirabegron, a drug approved to treat overactive bladder, activated brown fat in a small group of healthy women and had several other beneficial metabolic effects. Brown fat, or brown adipose tissue, is a form of fat that burns calories to generate heat. The research, led by Aaron Cypess, M.D., Ph.D., at the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), was published on Jan. 21 in the Journal of Clinical Investigation.

Fourteen women aged 18-40 of diverse ethnicities participated in the study at the NIH Clinical Center’s Metabolic Clinical Research Unit. For four weeks, each participant received daily doses of 100 mg of mirabegron, an amount exceeding the 50 mg maximum dosage approved by the U.S. Food and Drug Administration.

At four weeks, the participants’ brown fat activity had more than doubled since the first day, though their body weight and body mass stayed the same. Other changes included:

Increased resting energy expenditure
Higher levels of HDL (high-density lipoprotein) cholesterol — often referred to as “good” cholesterol — and bile acids, which help digest fats and regulate cholesterol
Improved processing and regulation of blood glucose (blood sugar)

Dr. Cypess and his colleagues previously found that a single dose of mirabegron increased brown fat activity and energy expenditure in healthy men, but the changes to HDL cholesterol, bile acids, and glucose processing were not seen. Of note, all these studies used dosages higher than currently approved by the FDA, as these doses were better able to show the drug’s potential metabolic benefits. However, the higher doses of mirabegron are linked to cardiovascular risk. Both male and female study participants did experience increased heart rates and blood pressure, which returned to normal after mirabegron treatment ended.

More research is needed to determine if mirabegron has metabolic benefits in a wider range of people, including older adults and people with obesity, and if similar drugs might produce these benefits without increasing cardiovascular risk. The present study, however, brings scientists closer to identifying a safe, effective way to activate brown fat and potentially treat metabolic disease.

Who

Aaron M. Cypess, M.D., Ph.D., is available to comment on this research.

Contact

To schedule an interview, please contact Lisa Yuan: niddkmedia@niddk.nih.gov, 301-496-3583

Article

O’Mara, A.E. et al. Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity. J Clin Invest. 2020; doi.org/10.1172/JCI131126

Funding

This work was supported by the NIDDK Division of Intramural Research and NIDDK grants DK075112, DK075116, DK071013, and DK071014.

About the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): The NIDDK, a component of the National Institutes of Health, conducts and supports research on diabetes and other endocrine and metabolic diseases; digestive diseases, nutrition and obesity; and kidney, urologic and hematologic diseases. Spanning the full spectrum of medicine and afflicting people of all ages and ethnic groups, these diseases encompass some of the most common, severe, and disabling conditions affecting Americans. For more information about the NIDDK and its programs, see https://www.niddk.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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