Knowing how brown fat cells develop may help fight obesity

March 14, 2013, University of Pennsylvania School of Medicine
This shows isolated interscapular brown fat tissue fixed and stained by hematoxylin and eosin. Hematoxylin stains DNA in the nucleus purple. The pinkish eosin stain is mitochondria (along with other cytoplasmic proteins), stained stronger in brown fat Credit: Sona Rajakumari and Jeff Ishibashi, Perelman School of Medicine, University of Pennsylvania

Brown fat is a hot topic, pardon the pun. Brown fats cells, as opposed to white fat cells, make heat for the body, and are thought to have evolved to help mammals cope with the cold. But, their role in generating warmth might also be applied to coping with obesity and diabetes.

The lab of Patrick Seale, PhD, at the Perelman School of Medicine, University of Pennsylvania, studies what proteins guide the development, differentiation, and function of . Seale and postdoctoral fellow Sona Rajakumari, PhD, along with Jun Wu from the Dana-Farber Cancer Institute, found that a protein switch called early B cell factor-2 (Ebf2) determines which developmental path fat precursor cells take – the brown vs. white cell trajectory.

"Brown fat cells are the professional heat-producing cells of the body," says Seale. Because of this they are protective against obesity as well as diabetes. Seale is an assistant professor of Cell and and a member of the Institute for Diabetes, Obesity and Metabolism. The investigators published their findings this week in Cell Metabolism.

The team showed that Ebf2 regulates the binding activity of PPAR-gamma, a protein that regulates differentiation of developing cell types and is the target of anti-diabetic drugs. Ebf2 affects PPAR-gamma's ability to determine if go down the white or brown fat cell path. The team surmises that Ebf2 may alter epigenetic proteins at brown fat genes to expose PPAR-gamma binding sites.

Brown fat cells are thought to counteract obesity by burning off stored in lipid, but cells store energy. Indeed, brown fat cells contain many smaller droplets of lipids and the most mitochondria (containing pigmented cytochromes that bind iron)of any cell type, which make them brown. Rajakumari conducted a genome-wide study of PPAR-gamma binding regions in white versus brown fat cells. She found that brown cell-specific binding sites also contained a DNA-recognition site for Ebf2 transcription factors and that Ebf2 was strongly expressed in brown fat cells only. When she overexpressed Ebf2 in precursor white fat cells they matured into brown fat cells. The brown fat cell status of the reprogrammed white fat cells was confirmed in that they consumed greater amounts of oxygen (a surrogate measure of heat production), had a greater number of mitochondria, and had an increased expression of genes involved in heat production, all characteristics of normal brown fat cells.

Rajakumari also looked at whether Ebf2 was required for brown fat cell development in animals by studying mice in which Ebf2 had been knocked out. Brown fat cells are typically located on the back, along the upper half of the spine and toward the shoulders. In contrast, excess abdominal concentrations of white fat cells are associated with metabolic dysfunction, insulin resistance, and heart disease.

She found that in late-stage embryos of these knockouts, white fat cells took the place of where brown fat cell reserves were in normal mice, indicating that stem cells differentiate into white fat in the absence of Ebf2.

Over the past few years, PET scan studies on glucose uptake by different tissues suggested that the amount of brown fat cells in people is inversely correlated with body mass index and age. This suggested that brown fat cells might play an unappreciated role in human metabolism. What's more, researchers started to suggest that "turning on" brown fat could be a new way to fight obesity and burn the extra stored lipids in white fat cells.

Ebf2 is the earliest known protein in the timeline of the development and differentiation of cells. "Many times the earlier in the developmental stage that a guiding protein is active, the more powerful it is in driving a certain process of differentiation," notes Seale. "Ebf2 is not really a readily druggable target, but perhaps a protein related to it is." Because Ebf2 is a transcription factor, it doesn't have a clear binding pocket, but the researchers propose that it might be possible to pharmacologically block or stimulate the interaction of Ebf2 with a partner protein.

Explore further: Calorie-burning brown fat is a potential obesity treatment, researchers say

Related Stories

Fat chance: Brown vs. white fat cell specification

May 14, 2008

In the May 15th issue of G&D, Dr. Bruce Spiegelman (Dana Farber Cancer Institute) and colleagues elucidate the molecular pathway that induces cells to become energy-burning brown fat cells as opposed to energy-storing white ...

A new candidate pathway for treating visceral obesity

May 6, 2012

Brown seems to be the color of choice when it comes to the types of fat cells in our bodies. Brown fat expends energy, while its counterpart, white fat stores it. The danger in white fat cells, along with the increased risk ...

Recommended for you

Scientists create 'Evolutionwatch' for plants

February 21, 2018

Using a hitchhiking weed, scientists from the Max Planck Institute for Developmental Biology reveal for the first time the mutation rate of a plant growing in the wild.

New tool tells bioengineers when to build microbial teams

February 21, 2018

Researchers at Duke University have created a framework for helping bioengineers determine when to use multiple lines of cells to manufacture a product. The work could help a variety of industries that use bacteria to produce ...

Triplefin fish found to have controlled iris radiance

February 21, 2018

A team of researchers with the University of Tübingen in Germany has found an example of a fish that is able to control light reflected from organs next to its pupils—a form of photolocation. In their paper published in ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.