Getting White Fat Cells To Burn Calories Could Be Way To Tackle Obesity

Featured Article
Academic Journal
Main Category: Obesity / Weight Loss / Fitness
Also Included In: Biology / Biochemistry;  Genetics
Article Date: 19 Mar 2013 - 0:00 PDT


US scientists have discovered a protein switch that decides whether precursor fat cells turn into white fat cells that store calories, or brown fat cells that burn calories. They suggest the fight against obesity and diabetes could learn some valuable clues from studying how this switch works. For example, might it be possible to use it to reprogram white fat cells to behave more like brown fat cells?

Patrick Seale, an assistant professor of Cell and Developmental Biology and a member of the Institute for Diabetes, Obesity and Metabolism of at the Perelman School of Medicine, University of Pennsylvania, and colleagues, write about their findings in the 14 March online issue of the journal Cell Metabolism.

Seale says in a statement:

"Brown fat cells are the professional heat-producing cells of the body."

And because of this they are protective against obesity as well as diabetes, he adds.

Brown Fat Burns Calories, White Fat Stores Them

Brown fat burns calories to generate heat, whereas white fat stores up calories in the all-too-obvious deposits that plague the growing numbers of overweight and obese people.

Carrying excess white fat around the abdomen is linked with metabolic dysfunction, insulin resistance, and heart disease.

Brown fat cells contain many smaller droplets of lipids and the most mitochondria (cellular power centers that "burn" the energy-containing lipids) of any cell type. Because the mitochondria contain pigments that bind iron, this makes the cells brown.

Until not very long ago, scientists believed the only humans who had brown fat were babies. More recently, they have discovered that adults have small but important amounts, in various parts of the body, and these probably evolved to help us cope with the cold.

Now they are suggesting the ability of brown fat cells to generate heat might also be applied to coping with obesity and diabetes.

That is because brown and white fat cells develop from the same type of precursor fat cell, and there is a biological switch that decides which of the two fat cells types a precursor cell becomes.

Perhaps there is a way to use this switch to "turn on" brown fat cells and burn the energy stored in white fat cells.

Protein Switch Controls Balance of Brown and White Fat Cells

Seale and colleagues found that the transcriptional factor Ebf2 (short for Early B Cell Factor 2), regulates the activity of a receptor protein called PPAR-gamma, which decides whether precursor fat cells (stem cells that become fat cells) turn into brown fat cells or white fat cells.

They found that Ebf2 regulates the binding activity of PPAR-gamma, and suggest it does this by altering epigenetic proteins at brown fat genes.

To arrive at the discovery they conducted a genome-wide study of binding regions in PPAR-gamma in white and brown fat cells.

They found that brown cell-specific binding sites were also primed to recognize the DNA pattern of Ebf2, which was strongly expressed only in brown fat cells.

So they decided to test what happens if Ebf2 is switched on in precursor white fat cells (fat stem cells that are already part way down the path of becoming white cells).

Over-Expressing Ebf2 in White Fat Precursor Cells Effectively "Reprogrammed" then Into Brown Cells

The researchers found that over-expressing Ebf2 in precursor white fat cells caused them to become brown fat cells. They double-checked their findings by testing the heat-producing ability of the "reprogrammed" white cells. They found they used up much more oxygen (a way of assessing heat production) than normal white cells, and contained greater quantities of mitochondria.

Genes known to be involved in heat production were also over-expressed in the reprogrammed white cells.

In other words, the reprogrammed white cells had all the hallmarks of normal brown fat cells.

The researchers then ran further tests in mice, to check whether Ebf2 was essential for brown fat development.

They bred mice to lack Ebf2 and found (in late-stage embryos) white fat deposits developing in places where normally only brown fat is found.

They conclude this suggests in the absence of Ebf2, fat stem cells differentiate only into white fat cells.

Manipulating Ebf2 Could Alter Metabolism By Changing Fat Cell Differentiation

Recent studies have suggested brown fat cells may play an important role in human metabolism: one that has not been well understood before.

Studies that have looked at PET scans of how different tissues in the body take up glucose, have shown that brown fat cell numbers are inversely related to age and body mass index (BMI). Thus people who are older or have a higher BMI, are more likely to have fewer brown fat cells than people who are younger, or have a lower BMI.

Perhaps, as this study suggests, by throwing a biological switch, it may be possible to reverse that balance, and reprogram white cells to be more like brown cells so they burn the lipids they carry instead of storing them.

In this study, by identifying Ebf2, the researchers have pinpointed a stage that is quite early in the development of stem cells into brown fat cells.

This in itself is important, because normally scientists find that the earlier in the development process the protein is active, the more power it has to drive the differentiation.

The downside is that because Ebf2 is a transcription factor, it doesn't have a clear binding site, so it can't be a drug target, but, as Seale notes, "perhaps a protein related to it is".

He and his colleagues suggest one approach might be to block or stimulate the action of Ebf2 with such a related protein.

In October 2012, researchers at the University of California, San Francisco (UCSF) revealed how they discovered another switch, based on the protein UCP1 that switches on fat burning in brown fat cells. They suggest this could be the target of drugs that increase calorie burning by keeping the switch in the "on" position.

However, as with the Ebf2 discovery, we are still a long way from knowing whether such an approach would be practical for weight control.

Written by Catharine Paddock PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

• Additional
• References
• Citations