Researchers discover pathway with implications for obesity

Jun 03, 2009 By Krishna Ramanujan
Researchers discover pathway with implications for obesity
Mature fat cells, known as adipocytes. Image: Ling Qi

( -- Cornell scientists have discovered how two related proteins and their roles in a key molecular pathway are critical to creating obesity-causing fat cells.

Targeting the proteins, known as IRE1alpha and XBP1, could hopefully lead to drug therapies to fight obesity, which affects one in three adults and contributes to heart disease, diabetes, some cancers and high blood pressure.

"We're trying to understand the mechanisms underlying the development of ," said Ling Qi, Cornell assistant professor of nutritional sciences and senior author of the paper, published in the June 3 issue of the journal (Vol. 9, No. 6). "The overall goal of my group is to find therapeutic strategies for treatment of obesity and obesity-associated complications."

The creation of fat cells involves a two-step process: Stem cells first develop into precursors of fat cells called pre-adipocytes, and then these cells develop into mature fat cells, called adipocytes.

The new study focuses on this second phase in which the pre-adipocytes experience a low level of stress in the , the organelle where new proteins are made and folded and then transported out for use by the cell. The stress caused by an accumulation of mis- or un-folded proteins is critical for the transition from pre-adipocytes to mature fat cells, the researchers found.

To counter the stress, cells activate IRE1alpha, a protein that resides in the endoplasmic reticulum and that senses unfolded proteins as a part of a cellular called the unfolded protein response. Qi and his colleagues created cells lacking IRE1alpha and demonstrated that these cells were unable to develop from pre-adipocytes into adipocytes. This evidence suggests that IRE1alpha is a key component of the pathway that leads to fat cell development, Qi said.

Activated IRE1alpha then converts the protein XBP1 into a new form. In its new configuration, XBP1 moves into the cell's nucleus, where it turns on genes that work to resume normal protein folding and balance to the endoplasmic reticulum. The researchers also found that loss of XBP1 interferes with the conversion of pre-adipocytes into mature fat cells.

The research is the first to show that the endoplasmic reticulum and the IRE1alpha-XBP1 pathway are involved in the genesis of fat cells, Qi said.

"The unfolded protein response keeps the balance of endoplasmic reticulum homeostasis," said Haibo Sha, the paper's lead author and a postdoctoral associate in Qi's lab. "If there are defects in the endoplasmic reticulum, then pre-adipocytes will not be able to differentiate into the adipocytes."

While lack of physical activity and overeating can lead to obesity, genetic mutations also can cause the condition. The researchers hope that drugs that target XPB1 or IRE1alpha may lead to treatment for obesity in the future, Qi said.

Provided by Cornell University (news : web)

Explore further: Supercharging stem cells to create new therapies

Related Stories

Unfolded proteins may protect cells from dying

Dec 26, 2006

When cells get stressed, their proteins go unfolded. It's a reaction with a straightforward name: the unfolded protein response. Now, new research from Rockefeller University shows that this phenomenon actually ...

Red pepper: Hot stuff for fighting fat?

Mar 05, 2007

Food scientists in Taiwan are reporting new evidence from laboratory experiments that capsaicin — the natural compound that gives red pepper that spicy hot kick — can reduce the growth of fat cells. The study is scheduled ...

Not all fat is created equal

Aug 27, 2008

A Temple University study finds fat in obese patients is "sick" when compared to fat in lean patients.

White tea -- the solution to the obesity epidemic?

May 01, 2009

Possible anti-obesity effects of white tea have been demonstrated in a series of experiments on human fat cells (adipocytes). Researchers writing in BioMed Central's open access journal Nutrition and Metabolism have shown ...

Human virus makes fat stem cells fatter

Oct 25, 2006

U.S. research showing how a human virus targets fat stem cells to produce more, fatter, fat cells is providing insights into the study of obesity.

Cellular stress causes fatty liver disease in mice

Dec 08, 2008

A University of Iowa researcher and colleagues at the University of Michigan have discovered a direct link between disruption of a critical cellular housekeeping process and fatty liver disease, a condition that causes fat ...

Recommended for you

Researchers reveal a genetic blueprint for cartilage

Jul 02, 2015

Cartilage does a lot more than determine the shapes of people's ears and noses. It also enables people to breathe and to form healthy bones—two processes essential to life. In a study published in Cell Re ...

User comments : 0

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.