Researchers at Vanderbilt University Medical Center and the VA Tennessee Valley Healthcare System have demonstrated in a small clinical study that “turning up the heat” on fat may help people lose weight and reduce their risk of obesity-related cardiovascular and metabolic disease.
In a research letter published recently in the journal Diabetes Obesity and Metabolism, the researchers reported the effects of infusing a hormone called B-type natriuretic peptide (BNP) in five white men, 18-40 years old.
Three of the men were obese but otherwise healthy, and two of them were “lean” (normal weight). All were U.S. veterans.
The BNP infusions stimulated expression of a gene associated with “beiging” called UCP1 (for uncoupling protein 1). Beiging refers to the conversion of white fat cells into fat-burning “beige” cells. In brown and beige fat cells, UCP1 is a marker for thermogenesis, dissipation of excess fat (stored chemical energy) as heat.
“This is the first study suggesting that BNP infusion in humans can induce the signaling mechanisms that cause adipocyte (fat cell) thermogenesis and beiging,” the researchers stated.
“Our results suggest a role for BNP in adipose tissue beiging in humans, representing a unique mechanism from current FDA-approved therapies for obesity.”
BNP works by a different mechanism than other weight-loss drugs currently approved for the treatment of obesity. BNP belongs to a family of protein hormones called natriuretic peptides that dilate blood vessels and cause the kidneys to excrete more salt and water.
Medications that augment the natriuretic peptide system are already on the market and are less expensive than the newer GLP-1 drugs. They include sacubitril/valsartan (marketed as Entresto, for heart failure) and phosphodiesterase inhibitors, which are prescribed for a wide range of conditions including erectile dysfunction and pulmonary arterial hypertension.
Some patients with obesity cannot take Ozempic, Mounjaro, or other GLP-1 receptor agonists for weight loss due to the expense (approximately $1,000 a month) or possible side effects, including nausea. Identifying other drugs for weight loss that work in different ways could potentially benefit patients, the VUMC researchers concluded.
The paper’s corresponding author, Ryan Ceddia, PhD, is a research instructor in the Division of Cardiovascular Medicine at VUMC.
The first author, Katherine Bachmann, MD, MSCI, is a former VUMC faculty member and staff physician/research scientist at the Nashville VA Medical Center, part of the U.S. Department of Veterans Affairs Tennessee Valley Healthcare System. She currently is a medical director at Amgen, which was not part of the study.
Other co-authors: Deepak Gupta, MD, MSCI, director of the Vanderbilt Translational and Clinical Cardiovascular Research Center; Sheila Collins, PhD, professor of Medicine at VUMC; and Thomas Wang, MD, former director of Cardiovascular Medicine at VUMC and current chair of Internal Medicine at UT Southwestern Medical Center in Dallas.
The study was supported by the VA Clinical Sciences Research and Development Program, National Institutes of Health grants UL1TR002243, R01HL145293, and T32DK007061, and the Vanderbilt Faculty Research Scholars program.
