Seeing through FOG: Shedding new light on fat

The Friends of GATA may sound like a social support group, but a new study reveals that they are a very different kind of support act – they are proteins that play a previously unknown role in the development of fat cells in the human body.

Known by the acronym of FOG, these special proteins not only help precursor cells called pre-adipocytes to become mature fat cells but they may also hold a key to fighting excessive weight gain by providing a way to prevent that process, according to a paper published in the Journal of Biological Chemistry.

Briony Jack, a doctoral student at the University of Sydney, and Professor Merlin Crossley, of the UNSW School of Biotechnology and Biomolecular Sciences, are investigating the gene regulatory proteins that control the complex chain of events involved in fat cell development.

"If we know how to turn on and off the genes that control fat development, we may be able to control obesity," says Professor Crossley.

"We’ve come a long way in recent years in getting to grips with what is happening right down there at the cellular level of fat development. This is another step along the way and the more we understand about the process, the better our chances of being able to offer interventions in the future that can help tackle the obesity epidemic in affluent nations."

Recent laboratory studies have shown that the proteins GATA1 and GATA2 – members of the GATA family that play a pivotal role in the development and growth of many different kinds of cells – are present in pre-adipocytes but the genes that control their production must be switched off before those cells can go on to mature.

The new study reveals that the two GATA proteins are helped by FOG1 and FOG2, and these two recruited proteins are also suppressed when the fat cells mature. Experiments with mutant forms of these proteins confirmed that the GATA and FOG groups work together in normal fat cell development.

"If future treatments for obesity involve preventing fat cells from maturing, this new study gives us a much better insight in what we’ll need to do to make that happen," says Professor Crossley.

"Over the past 50 years we’ve been identifying the DNA-binding proteins that are critical in bacteria, then the ones in yeast, then in drosophila, worms, and in all the different human tissues – starting with blood but moving to muscle, nerve and, in the last 5 years or so, fat.

"Ten years ago we knew that DNA-binding proteins recognizsed the beginnings of genes and either blocked and facilitated their expression.

"We have also worked out what the DNA-binding proteins do. Originally it was thought they sat there like road blocks. We now know they control the folding of the gene to open or close it. They probably also deliver the gene to special factories in the nucleus where the gene is read. The co-factors like FOG are probably involved in the folding or the delivery.

"In 10 years time we will also know the biological signals – hormones or small chemical signals – that naturally control these DNA-binding proteins and thereby control the processes. If we can mimic these signals then we too should be able to artificially control the process therapeutically."

(Source: University of NSW: Journal of Biological Chemistry)