Have you ever heard of calorie-burning "brown fat"? Scientists say this good form of human fat can be produced experimentally from muscle precursor cells in mice, and could be a weapon in the battle against obesity.
Brown fat burns calories and releases energy, unlike "bad" white fat that simply stores extra calories.
A previously known molecular switch, PRDM16, regulates the creation of brown fat from immature muscle cells.
The PRDM16 trigger "is very powerful at what it does," said Dana-Farber Cancer Center's Dr. Bruce Spiegelman, who is also a professor of cell biology at Harvard Medical School.
PRDM16 regulates the creation of brown fat from immature muscle cells. The team led by Spiegelman and Patrick Seale, PhD also determined that the process is a two-way street: Knocking out PRDM16 in brown fat cells can convert them into muscle cells.
Spiegelman says the two-way street is, for now, an "experimental lab trick" for which he currently envisions no practical applications.
But the surprising and great news from the study results: the muscle precursor cells known as "satellite cells" are able to give birth to brown fat cells under the control of PRDM16.
Further testing will be done on two possible applications for this finding:
- To see if drugs that rev up PRDM16 in mice -- and potentially, in people -- could convert white fat into brown fat and thereby treat obesity.
- To transplant brown fat cells into an overweight person to turn on the calorie-burning process.
"I think we now have very convincing evidence that PRDM16 can turn cells into brown fat cells, with the possibility of combating obesity," Spiegelman said in a news release.
The study was published in the Aug. 21 issue of Nature, which has an accompanying article on a different trigger of brown fat production, a molecule called BMP7.
Barbara Cannon, an internationally recognized researcher in the biology of fat cells at the University of Stockholm, said that the two reports "take us a step closer to the ultimate goal of promoting the brown fat lineage as a potential way of counteracting obesity."
ABSTRACT:
BOSTON - Aug. 20, 2008 - A study by researchers at the Joslin Diabetes Center has shown that a protein known for its role in inducing bone growth can also help promote the development of brown fat, a "good" fat that helps in the expenditure of energy and plays a role in fighting obesity.
"Obesity is occurring at epidemic rates in the U.S. and worldwide and that impacts the risk and prognosis of many diseases," said Yu-Hua Tseng, Ph.D. an Assistant Investigator in the Joslin Section on Obesity and Hormone Action and lead author of the paper published in the August 21 issue of Nature. "We hope this study can be translated into applications to help treat or prevent obesity."
Tseng noted that obesity is a major risk factor for type 2 diabetes and is closely linked to the metabolic syndrome, a collection of medical problems associated with insulin resistance that can lead to an increased risk of atherosclerosis, the buildup of plaque in coronary arteries that leads to heart attack and stroke.
In laboratory studies of mouse cells, Tseng and her colleagues identified that a bone-inducing protein called BMP-7 drives precursor cells that give rise to mature brown fat cells. According to Tseng, there are two main types of fat cells in the body - white and brown.
"White fat cells are the 'conventional' form of fat designed to store energy. By contrast, the main role of brown fat is to burn calories by generating heat. Brown fat cells largely disappear by adulthood in humans, but their precursors still remain in the body," Tseng explained.
A 2005 Joslin study by Dr. Tseng and colleagues discovered genes that control the creation of the precursor cells of brown fat. Another more recent 2007 Joslin study led by C. Ronald Kahn, M.D., head of the Joslin Section on Obesity and Hormone Action and also a co-author of the current Nature study, found clusters of brown fat cells dispersed between bundles of muscle fibers in an obesity-resistant strain of mice.
Now, this latest study identified BMP-7 as the protein capable of inducing the formation and function of brown fat cells. According to the paper, delivery of BMP-7 into mice using adenovirus as a vector resulted in an increase in the development of brown fat tissue. In one of the experiments, the mice that developed brown fat tissue gained less weight than those that did not. In another experiment, mice that received injections of progenitor cells - similar to stem cells - that had been pre-treated with BMP-7 also developed additional brown fat tissue.
The study sought to address a fundamental question in adipocyte biology, namely what controls the development of fat depots. BMPs are a family of proteins known to regulate organ formation during embryonic development. In this study, Dr. Tseng and her colleagues proposed that different members of BMPs determine brown versus white fat cell fate. Scientists hope that improved knowledge of fat development will lead to new drugs or therapeutic approaches to fight obesity.
"Diet and exercise are still the best approaches for weight reduction in the general population," Tseng said. "However, for people who are genetically predisposed to obesity, these approaches may have very little effect."
"As we learn more about the controls of brown fat development, medical interventions to increase energy expenditure by brown fat inducing agents, such as BMP-7, may provide hope to these individuals in losing weight and preventing the metabolic disorders associated with obesity," she said.
