Brown fat cell discovery opens new doors for obesity treatment
The human body carries different types of fat cells, and some of them are more desirable than others. White fat stores our surplus energy as lipids that give rise to love handles and beer bellies, whereas brown fat burns off calories to generate heat and keep us warm. Much research into obesity of late has focused on ways the body might be made to produce more brown fat as a way of fighting weight gain, and scientists have now made a key advance in this area by discovering a previously unknown source of its production.
The research carried out at Boston's Joslin Diabetes Center focuses on brown fat cells as well as another, third cell type called beige fat, which like brown contains more mitochondria and burns away calories in response to cold temperatures, keeping the body warm. The scientists set out to understand where these "good" types of fat cells come from, in hope of unearthing new targets for obesity therapy.
“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,” said senior author Yu-Hua Tseng. “And yet, the precise origins of cold-induced brown adipocytes and mechanisms of action have remained a bit of a mystery.”
These brown and beige fat cells had been thought to originate via a set of cells that express a receptor called Pdgfrα, though previous research had given scientists reason to suspect there are other factors at play. To explore this possibility, the team used a technique called single-cell sequencing to study the cellular composition of brown fat in mice kept at different temperatures, for different lengths of time.
This revealed that cells expressing the receptor Pdgfrα were indeed a source of the brown fat cells, but the data also revealed another set of cells performing the same role. These were found to be smooth muscle cells expressing another type of receptor, called Trpv1, which is a protein that has been found in a variety of cell types and is known to sense stimuli relating to pain and heat sensation.
Digging further into the mechanisms behind this, the team confirmed these smooth muscles cells were acting as a source for the brown fat cells, particularly when the mice were exposed to cold temperatures. Further experiments demonstrated that the cold temperatures also saw the smooth muscle cells become a source of beige fat cells, further boosting the potential of the Trpv1 receptor as a focal point for advanced obesity treatments.
“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,” says Tseng.
While studies have shown that cold exposure can cause the body to produce more brown fat cells rather than white ones, scientists like Tseng hope to use alternative means to trigger these conversions in humans. The possibilities include fish oils, targeting certain proteins as a type of "fat switch" or even "fat transplants." Promisingly, the scientists note that the Trpv1 receptor can detect and respond to a variety of stimuli, including compounds in chili peppers, so there are possibilities that don't include subjecting humans to freezing temperatures or other uncomfortable sensations.
“Further studies are now planned to address the role of the Trpv1 channel and its ligands and whether it is possible to target these cells to increase numbers of thermogenic adipocytes as a therapeutic approach towards obesity," says Tseng.
The research was published in the journal Nature Metabolism.
Source: Joslin Diabetes Center