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Small protein may have big role in making more bone and less fat
Date:7/1/2008

A small protein may have a big role in helping you make more bone and less fat, researchers say.

"The pathways are parallel, and the idea is if you can somehow disrupt the fat production pathway, you will get more bone," says Dr. Xingming Shi, bone biologist at the Medical College of Georgia Institute of Molecular Medicine and Genetics.

He's found the short-acting protein GILZ appears to make this desirable shift and wants to better understand how it does it with the long-term goal of targeted therapies for osteoporosis, obesity and maybe more.

"Osteoporosis and obesity are two major public health problems, but people have no idea whether they have a connection," says Dr. Shi. Bone and fat do have a common source: both are derived from mesynchymal stem cells. Bone loss and fat gain also tend to happen with age and with use of the powerful, anti-inflammatory steroid hormones glucocorticoids. "When you age, your bone marrow microenvironment changes; the balance between the bone and fat pathway is broken," says Dr. Shi, a faculty member in the MCG Schools of Medicine and Graduate Studies. "You have more fat cells accumulate."

"The bones of elderly people or those who take glucocorticoids are yellow inside instead of red," he says. And it gets worse: in a classic vicious cycle, the more fat, the more cytokines that stimulate production of bone-destroying osteoclasts and inhibit bone-forming osteoblasts. He recently showed that even the stem cells change with age: their numbers and their ability to differentiate decrease.

Weight gain and bone loss are established side effects of glucocorticoids, whose wide-ranging uses include treatment for arthritis, asthma, infections and organ transplants. Ironically, glucocorticoids also induce a short burst of GILZ. GILZ, in turn, inhibits the transcription factor PPAR2, called the master regulator of adipogenesis, or fat production, as well as CCAAT/enhancer-binding proteins tha
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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
Source:Eurekalert  

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