Brown fat, also known as brown adipose tissue, is a type of body fat that is activated when we get cold. It produces heat to help maintain our body temperature in cold conditions. Brown fat has been a topic of interest as researchers find it is able to use regular body fat as fuel and exercise may stimulate hormones that activate it. Recent research from the Joslin Diabetes Center reports that a new source of energy expending brown fat cells has been identified. Their findings may lead to potential therapeutic strategies for obesity.

Their study is published in the journal Nature Metabolism, in a paper titled, “Vascular smooth muscle-derived Trpv1+ progenitors are a source of cold-induced thermogenic adipocytes.”

The actual mechanisms by which brown fat may contribute to better health are still unclear, but there are some clues. For example, brown fat cells consume glucose in order to burn calories, and it’s possible that this lowers blood glucose levels, a major risk factor for developing diabetes.

The researchers reported that the expression of the receptor called Trpv1 (temperature-sensitive ion channel transient receptor potential cation subfamily V member 1) may be the key to unlocking this energy.

Trpv1 is best known for its function in nociceptive (“pain receptor”) neurons, detecting noxious heat and pain. It is activated by heat and capsaicin, the pungent compound in chili peppers.

“Brown adipose tissue (BAT) and beige fat function in energy expenditure in part due to their role in thermoregulation, making these tissues attractive targets for treating obesity and metabolic disorders,” wrote the researchers. “While prolonged cold exposure promotes de novo recruitment of brown adipocytes, the exact sources of cold-induced thermogenic adipocytes are not completely understood. Here, we identify transient receptor potential cation channel subfamily V member 1 (Trpv1)+ vascular smooth muscle (VSM) cells as previously unidentified thermogenic adipocyte progenitors.”

“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,” explained senior author Yu-Hua Tseng, PhD, senior investigator in integrative physiology and metabolism at the Joslin Diabetes Center and an associate professor of medicine at Harvard Medical School. “And yet, the precise origins of cold-induced brown adipocytes and mechanisms of action have remained a bit of a mystery.”

The team initially investigated the general cellular makeup of brown adipose tissue from mice housed at different temperatures and lengths of time. “Single-cell RNA sequencing analysis of interscapular brown adipose depots reveals, in addition to the previously known platelet-derived growth factor receptor (Pdgfr)α-expressing mesenchymal progenitors, a population of VSM-derived adipocyte progenitor cells (VSM-APC) expressing the temperature-sensitive cation channel Trpv1,” added the researchers. “We demonstrate that cold exposure induces the proliferation of Trpv1+ VSM-APCs and enhances their differentiation to highly thermogenic adipocytes.”

Co-author Matthew D. Lynes, PhD, research associate, Joslin Diabetes Center and instructor in medicine, Harvard Medical School, noted that single-cell sequencing combined with advanced data analysis techniques allowed the researchers to make predictions in silico about the development of brown fat. “By validating these predictions, we hope to open up new cellular targets for metabolic research,” Lynes stated.

Further study with mouse models confirmed that the Trpv1-positive smooth muscle cells initiated the brown energy-burning version of fat cells, especially when exposed to cold temperatures. Further observation revealed that the Trpv1-positive cells were a source for beige fat cells that appear in response to cold in white fat.

“The identification of Trpv1-expressing cells as a new source of cold-induced brown or beige adipocytes 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,” added Tseng.

The researchers are now planning to determine the role of the Trpv1 channel and its ligands and whether it will be possible to target the cells to increase the numbers of thermogenic adipocytes as a therapeutic strategy for obesity.

1 COMMENT

  1. “We demonstrate that **cold exposure induces the proliferation of Trpv1+ VSM-APCs and enhances their differentiation to highly thermogenic adipocytes.” Given Trpv1 is involved in both pain and heat sensation, does this mean that people with more brown fat may be more sensitive to pain? Particularly epigastric pain?