May 4, 2021

Uncovering the origins of brown fat

At a Glance

  • Researchers identified previously unknown origins of brown fat, which burns energy to create heat.
  • Methods to produce more brown fat or increase its activity may provide new treatments for obesity.
Round mitochondria of various sizes in a brown fat cell Brown fat is different from white fat because of its many mitochondria, shown here, with their extensive internal membranes. Mitochondria can burn energy to generate heat and raise body temperature. Don W. Fawcett, Fawcett’s “The Cell” 2nd Ed., CIL:11426, Creative Commons License (

More than two-thirds of adults in the U.S. are currently overweight or obese. Too much white fat, a characteristic of these conditions, increases the risk of type 2 diabetes, high blood pressure, and other diseases. Excess weight can also affect the outcomes of disease. For example, it raises the likelihood of being hospitalized with COVID-19.

While white fat stores extra energy, another type of fat called brown fat—and the related beige fat—breaks down blood sugar and fat molecules to create heat and help maintain body temperature. Researchers have been studying brown and beige fat as potential targets for treating obesity. But the identity of the cells in the adult body that produce brown fat has remained unclear.

In a pair of new studies funded in part by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), researchers used mice and human tissue samples to search for the origins of brown fat. The results from the studies were published on April 12, 2021, in Nature Metabolism.

One team, led by Dr. Patrick Seale from the University of Pennsylvania, focused on brown fat found in the tissue that surrounds some large blood vessels. This is called perivascular adipose tissue (PVAT). They found that much of the PVAT during early development in mice derived from cells called fibroblasts. They also found new brown fat cells in the PVAT of adult mice that formed from a special type of smooth muscle cell.

The researchers found parallel types of cells in PVAT tissue taken from people. These cells shared molecular properties with the mouse cells that produced brown fat. Such cells might provide targets for drugs designed to boost brown fat production in humans.

Another team, led by Drs. Matthew Lynes and Yu-Hua Tseng from the Joslin Diabetes Center, traced the cells that can produce brown fat in mice. The researchers performed RNA sequencing on more than 105,000 single cells in brown fat from mice exposed to different temperatures. Different cell types produce distinct sets of RNA, so this technique can be used to distinguish and characterize each individual cell.

Mice living at cold temperatures for a week began to produce more brown fat. The team tracked the origins of these new brown fat cells to a type of smooth muscle cell that hadn’t previously been known to produce brown fat. Notably, these muscle cells expressed a receptor called Trpv1. Trpv1, among other things, can help cells sense temperature and compounds—like capsaicin in chili peppers—that cause a hot sensation. Seale’s team also found this receptor on cells that formed brown fat in adult mice.

“The capacity of brown and beige fat cells to burn fuel and produce heat, especially upon exposure to cold temperatures, have long made them an attractive target for treating obesity and other metabolic disorders,” Tseng says. “The identification of Trpv1-expessing cells as a new source of [these cells] suggests it might be possible to refine the use of cold temperatures to treat obesity by developing drugs that recapitulate the effects of cold exposure at the cellular level.”

—by Sharon Reynolds

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References: Vascular smooth muscle-derived Trpv1+ progenitors are a source of cold-induced thermogenic adipocytes. Shamsi F, Piper M, Ho LL, Huang TL, Gupta A, Streets A, Lynes MD, Tseng YH. Nat Metab. 2021 Apr 12. doi: 10.1038/s42255-021-00373-z. Online ahead of print. PMID: 33846638.

Defining the lineage of thermogenic perivascular adipose tissue. Angueira AR, Sakers AP, Holman CD, Cheng L, Arbocco MN, Shamsi F, Lynes MD, Shrestha R, Okada C, Batmanov K, Susztak K, Tseng YH, Liaw L, Seale P. Nat Metab. 2021 Apr 12. doi: 10.1038/s42255-021-00380-0. Online ahead of print. PMID: 33846639.

Funding: NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); American Diabetes Association; Chan Zuckerberg Foundation; Harvard Stem Cell Institute.