Can brown fat could fight obesity?
The obesity epidemic in all age groups has focussed public attention on adipose tissue or fat. We know how fat cells work, but not, until recently, where they come from.
We know that "good" fat cells produce soluble substances called adipokines, involved in the positive regulation of metabolism. "Bad” fat cells secrete pro-inflammatory substances called cytokines that start the ball rolling for insulin resistance, with all its far-reaching consequences.
It is public knowledge that visceral fat (the fat that surrounds the vital organs of your body) and that laid around the tummy is associated with much higher risk for diabetes, high cholesterol, heart disease including hypertension. Subcutaneous fat (fat under the skin) does not forecast similar risks.
All this applies to white fat. But there is a different type of fat, brown fat, which has a more limited distribution than ordinary white fat. Brown fat is proportionately more widespread in newborns, and recedes to limited locations in adults, and is increased (at least in mice) by low environmental temperatures.
Brown fat is brown because of its high number of mitochondria, the cellular micro-engines which are involved in energy generation. While white fat stores energy, brown fat generates heat by burning off fatty acid.
Two recent papers have explored the cellular origins of white and brown fat. To everyone’s surprise, they appear to have different origins.
A team of scientists1 have found that brown fat is derived from the same parental cells as skeletal muscle. If genes that encode for proteins called PPAR-gamma and PRDM16 are turned on a parental cell, it becomes a brown fat cell. If muscle determination factors are expressed instead, skeletal muscles are the result.
"Brown fat” derived from white fat under condition of increased adrenaline secretion ( as in exposure to a very cold environment) has a different gene expression profile than "real” brown fat. The relative contribution of this pathway to brown fat generation is unknown.
A second team of scientists2 investigated the origins of white fat cells and how they are replenished. Apparently, most white fat cells derive from parental cells called pericytes which look like octopi and are an integral part of the outside layer of blood vessels. They are in contact with the tissue in which the blood vessels are embedded. These cells are destined to become white fate cells in embryonic life or shortly thereafter. A set of fate-determining factors including PPAR-gamma characterise these parental cells. Their further differentiation is regulated by a set of factors, some of which, like insulin, are also required for brown fat development while others (e.g. distinct BMP transcription factors) are not.
This research leads us to ask: Is the dream of controlling or reducing obesity by turning white fat to brown as far-fetched as that of ancient alchemist’s of turning lead to gold? I don’t think so!
1 Seale P et al Nature 454: 96, 2008
2 Tang W et al Science 322:583, 2008