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System in brain -- target of class of diabetes drugs -- linked to weight gain
Date:5/1/2011

CINCINNATIUniversity of Cincinnati (UC) researchers have determined why a certain class of diabetes drugs leads to weight gain and have found that the molecular system involved (PPAR-γ found in the brain) is also triggered by consumption of high-fat foods.

The study could lead to the modification of existing diabetes therapies and even dietary recommendations to limit the action of this nuclear receptor in the brain.

The research, led by Randy Seeley, PhD, UC professor and Donald C. Harrison Endowed Chair in Medicine, appears as an advanced online publication May 1, 2011, in the journal Nature Medicine.

PPAR-γ is found in white adipose (fat) tissue where it regulates the production of fat cells. This new research describes an important role for PPAR-γ in the brain.

PPAR-γ is the target of a class of diabetes drugs called TZDs (thiazolidinediones). This class of drugs reduces blood glucose levels but also causes considerable weight gain. That weight gain, Seeley says, makes many patients reluctant to use these therapies particularly since many are already trying to lose weight to improve their diabetes.

Seeley and his team set out to determine whether or not the brain's PPAR-γ system was responsible for the weight gain associated with TZDs. The team also wanted to learn if this system in the brain was activated by a high-fat diet.

To do so, they used animal models to test how the class of drugs interacted with the brain PPAR-γ system. They found that by giving TZD drugs in the same manner that people take them, rats gained weight. This was because the drugs activated PPAR-γ in the brain. Thus, weight gain associated with this class of drugs may not be a result of action of PPAR-γ in fat as had been previously thought, but rather a result of a change in activity in parts of the brain known to regulate appetite.

Seeley's team went on to also
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Contact: Dama Ewbank
dama.ewbank@uc.edu
513-558-4519
University of Cincinnati Academic Health Center
Source:Eurekalert

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