A drug designed to mimic some of the metabolic effects of cold increased calorie burning in a small human study, but not in the way researchers expected. Credit: Shutterstock

In a small study, a drug increased calorie burning without clearly switching on brown fat, the heat-producing tissue scientists hope to harness to help people lose weight.

Brown fat burns energy to keep us warm, and researchers hope a drug could put that ability to work against obesity. In a small human study, the drug fenoterol increased the body’s energy use without clearly activating brown fat, leaving researchers unsure where the extra energy was being spent.

The prospect of increasing energy expenditure is appealing because the body often responds to weight loss by using less energy. Current weight loss drugs reduce appetite, addressing the other side of that balance.

“Ideally, we could combine a reduction in appetite with an increase in energy expenditure,” says Professor Matthias Betz of the University of Basel and University Hospital Basel. “But first we need a better understanding of how brown adipose tissue is regulated.”

Cold activates brown adipose tissue and increases energy expenditure. The bright areas in the FDG-PET/CT scan show where the tissue takes up particularly large amounts of glucose. Credit: Matthias Betz

Only cold clearly activates brown fat

Brown adipose tissue, another name for brown fat, naturally becomes active in response to cold. People with active brown fat also tend to be leaner and have a more favorable metabolic profile. Those observations have encouraged researchers to look for medicines that could reproduce the effect of cold.

Betz and his colleagues investigated whether they could achieve that effect by stimulating beta2 adrenergic receptors, proteins that receive signals in cells. Fenoterol stimulates these receptors, allowing the team to test whether this particular signaling route could activate human brown fat. The findings were published in Cell Metabolism.

Prof. Dr. Matthias Betz leads a research group at the Department of Clinical Research at the University of Basel and is a senior physician in endocrinology and diabetology at University Hospital Basel. By closely linking academic research and clinical practice, his team studies fundamental questions about metabolism that could point to new therapeutic approaches. Credit: Eleni Kougionis, University of Basel

Eleven healthy volunteers underwent both mild cold exposure and treatment with fenoterol. The researchers measured how much energy their bodies used and assessed brown fat activity with PET/CT scans. Both interventions increased energy expenditure, but only cold clearly activated brown fat. After cold exposure, the tissue took up substantially more glucose, a sugar it can use for fuel, than it did after fenoterol treatment.

“We were surprised that energy expenditure increased strongly with fenoterol even though we could not detect a comparable activation of brown fat,” says Betz. “Our study shows that an increase in energy expenditure does not automatically mean that brown fat has been activated.”

Other tissues may explain fenoterol’s effect

The additional energy consumption triggered by fenoterol may instead involve skeletal muscle or white fat, which mainly stores energy. The study did not establish which tissues or processes were responsible.

Analyses of human tissue also suggest that fully activating brown fat may require several receptors or biological signals to work together. That possibility makes stimulating a single receptor a less straightforward route to a treatment than researchers had hoped.

Reference: “Beta2-adrenergic stimulation by fenoterol increases energy expenditure without activating human brown adipose tissue” by Laila Maria Füchtbauer, Jaël Rut Senn, Carole Stéphanie Baumann, Anninja Lea Isenrich, Taylah Lea Gaynor, Rahel Schläfli, Anand Kumar Sharma, Carla Horvath, Claudia Irene Maushart, Adhideb Ghosh, Kirsi A. Virtanen, Tobias Fromme, Alin Chirindel, Damian Wild, Søren Nielsen, Christian Wolfrum and Matthias Johannes Betz, 12 August 2026, Cell Metabolism.
DOI: 10.1016/j.cmet.2026.07.012

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