Scientists discover switch that turns white fat brown

Scientists have discovered a biological switch that gives energy-storing white fat the characteristics of energy-burning brown fat. The findings could lead to new strategies for treating obesity.

The animal study by researchers at The Ohio State University Medical Center shows that the change is due to the activation of a nerve and that begins in the hypothalamus, an area of the brain involved in , and ends in white . This pathway, called the hypothalamic-adipocyte axis, also induces brown-fat-like cells within masses of white fat.

The white-to-brown fat transformation occurs when animals are placed in an enriched environment, one with a variety of social and physical challenges.

The findings are published in the September issue of the journal .

"One of the holy grails of obesity therapy is to understand how to switch white fat to brown fat, and this study describes a new way to do exactly that," says study leader and researcher Dr. Matthew J. During, professor of neuroscience, of neurological surgery and of , immunology and . "Our findings suggest that we can potentially induce this transformation by modifying our lifestyle or by pharmacologically activating this brain-fat pathway."

Lead and corresponding author Dr. Lei Cao, assistant professor of molecular virology, immunology and medical genetics, notes that obesity is caused by a chronic energy surplus that is stored as lipid in white fat. "Increasing the output of energy is always attractive for , which is why the discovery of brown fat in adult humans caused much excitement a few years ago," she says.

"However, up to now the only known approach to inducing brown fat has been through exposure to chronic cold. Our research reveals a novel way of doing this without cold exposure. We show that animals living in an enriched environment become lean and resistant to diet-induced obesity, even in the presence of unlimited food." In 2010, During, Cao and their colleagues showed in a paper published in the journal Cell that this enrichment effect by itself curbed cancer growth in animals.

The current study used a similarly designed environment, with 15-20 mice housed in large containers equipped with running wheels, tunnels, huts, wood toys, a maze, and nesting material, in addition to unlimited food and water. Control mice were housed in groups of five in smaller, standard laboratory containers without toys but with unlimited food and water.

Key findings include the following:

  • Enriched animals showed a significant reduction in abdominal white fat mass (49 percent less than controls).
  • Exercise (running in a wheel) alone did not account for the changes in body composition and metabolism of enriched animals.
  • Fed a high fat diet (45 percent fat), enriched animals gained 29 percent less weight than control mice and remained lean, with no change in food intake. Enriched animals also had a higher body temperature, suggesting that greater energy output, not suppressed appetite, led to the resistance to obesity.
In brief, During and Cao explained that the enriched environment stimulates production of a protein called brain-derived neurotrophic factor (BDNF) in the hypothalamus. The normal function of BDNF includes helping control food intake and energy balance.

The increased BDNF triggers sympathetic nervous signals to white fat masses in the body. These signals activate genes specific for brown fat such as Prdm16 and Ucp1, and suppress white-fat genes such as Resn. Blocking BDNF, on the other hand, inhibits or reverses the browning effect.

Overall, the study shows that environmental enrichment has an anti-obesity effect that involves the transformation of white fat to . That happens through a central mechanism called the hypothalamic-sympathoneural-adipocyte axis – environmental enrichment stimulates the hypothalamus to produce the protein BDNF, increasing sympathetic nerve output to white fat, causing the "browning" of and the burning of stored energy.

Next, During, Cao and their colleagues plan to identify which components of environmental enrichment – sensory, cognitive, motor or social stimulation – are essential for the browning effect.

Provided by Ohio State University Medical Center

5 /5 (5 votes)

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 ...

Housing upgrade shrinks tumors in mice with cancer

Jul 08, 2010

When mice with cancer get a boost in their social life and an upgrade in living conditions, their tumors shrink, and their cancers more often go into spontaneous remission Reported in the July 9th issue of the journal Cell, these ...

Control of blood vessels a possible weapon against obesity

Jan 07, 2009

Mice exposed to low temperatures develop more blood vessels in their adipose tissue and metabolise body fat more quickly, according to a new study from Karolinska Institutet. Scientists now hope to learn how to control blood ...

Recommended for you

A new way to prevent the spread of devastating diseases

5 hours ago

For decades, researchers have tried to develop broadly effective vaccines to prevent the spread of illnesses such as HIV, malaria, and tuberculosis. While limited progress has been made along these lines, ...

New molecule allows for increase in stem cell transplants

5 hours ago

Investigators from the Institute for Research in Immunology and Cancer (IRIC) at the Université de Montréal have just published, in the prestigious magazine Science, the announcement of the discovery of a new molecule, the fi ...

Team explores STXBP5 gene and its role in blood clotting

8 hours ago

Two independent groups of researchers led by Sidney (Wally) Whiteheart, PhD, of the University of Kentucky, and Charles Lowenstein, MD, of the University of Rochester, have published important studies exploring the role that ...

User comments