CAMBRIDGE, Mass. (June 30, 2004) — Obesity researchers made an intriguing discovery in 2001 when they found that large doses of a particular fat-cell protein, adiponectin, caused obese mice to lose weight. Although these findings placed adiponectin in the center of the search to one day develop an anti-obesity drug, the exact mechanism of the protein remains a mystery, as do the other potential cellular players.
The picture became clearer last week when a team led by Whitehead Member Harvey Lodish identified another key player in fat metabolism — a receptor protein for adiponectin. This protein, T-cadherin, is located on cell surfaces in blood vessel linings, the heart, and muscle tissue.
“Discovering a protein that adiponectin interacts with now provides us a way to learn more about adiponectin itself,” says Christopher Hug, a visiting scientist in the Lodish lab and lead author on the research paper which appeared in the June 21 early online edition of the journal Proceedings of the National Academy of Sciences.
In particular, this may eventually enable scientists to develop a molecule that mimics adiponectin. “This is one of our long term goals,” says Hug, “since we saw earlier how effective the molecule is in treating obesity in mice. This may one day help us possibly counteract type 2 diabetes.”
An additional paper from the Lodish lab has added yet another layer to scientists’ understanding of adiponectin.
Postdoctoral researcher Guang Wong has just discovered a new protein, mCTRP2, which, like adiponectin, increases fatty acid oxidation. And because this new protein belongs to a larger class of related proteins, this implies that metabolic regulation may be far more complex than previously thought.
“It has opened up a huge area of investigation for many years to come,” says Wong.
Whitehead Institute for Biomedical Research is a nonprofit, independent research and educational institution. Wholly independent in its governance, finances and research programs, Whitehead shares a close affiliation with Massachusetts Institute of Technology through its faculty, who hold joint MIT appointments.
© 2004 Whitehead Institute
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Wong GW, Wang J, Hug C, Tsao TS, Lodish HF.
A family of Acrp30/adiponectin structural and functional paralogs.
Proc Natl Acad Sci U S A. 2004 Jul 1 [Epub ahead of print]
Hug C, Wang J, Ahmad NS, Bogan JS, Tsao TS, Lodish HF.
T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin.
Proc Natl Acad Sci U S A. 2004 Jun 21 [Epub ahead of print]
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