The body contains two types of fat cells: white and brown. While white fat stores excess calories until they're needed by the body, brown adipocytes actually burn fat by turning it into heat.
Researchers at Harvard Medical School and Beth Israel Deaconess Medical Center have demonstrated that the transcription factor IRF4 (interferon regulatory factor 4) plays a key role in brown fat's thermogenic process, regulating energy expenditure and cold tolerance.
"The discovery several years ago that brown fat plays an active role in metabolism suggested that if we could manipulate the number or activity of these fat cells, we could force our bodies to burn extra calories," said the study's senior author, Evan Rosen.
"Now that we have identified a major factor driving this process, we can look for new approaches to exploit this for therapeutic benefit," said Rosen.
Turned on by low temperatures and by certain hormones and drugs, including epinephrine, brown fat generates heat through the actions of a group of genes collectively termed the thermogenic gene expression programme, the best known of which encodes uncoupling protein 1 (UCP1).
UCP1 dissipates, or wastes, energy in the mitochondria of brown fat cells, causing heat generation as a byproduct.
In the study, led by first author Xingxing Kong, a postdoctoral fellow in the Rosen lab, scientists hypothesised that in addition to serving as a key regulator of lipolysis, IRF4 might also play a direct thermogenic role in brown fat.
Experiments in mouse models confirmed their hypothesis, demonstrating that IRF4 is sufficient to promote increased thermogenic gene expression, energy expenditure and cold tolerance.
"With this new discovery of IRF4's key transcriptional role, perhaps we can identify new drug targets that directly affect this pathway, which might be more specific than simply giving epinephrine-like drugs, which drive up heart rate and blood pressure," said Rosen.