PPAR-gamma is found in white adipose (fat) tissue where it regulates the production of fat cells.
PPAR-gamma 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 makes many patients reluctant to use these therapies particularly since many are already trying to lose weight to improve their diabetes, said Randy Seeley.
Seeley and his team set out to determine whether or not the brain's PPAR-gamma system was responsible for the weight gain associated with TZDs.
They 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-gamma 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-gamma in the brain.
Thus, weight gain associated with this class of drugs may not be a result of action of PPAR-gamma 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 show that high-fat diets result in activation of the brain PPAR-gamma system.
Experiments in which the activity of the brain PPAR-gamma system was limited resulted in less weight gain when animals were exposed to a high-fat diet similar to diets of many Americans.
"This work helps us understand the complex relationship between our fat, our appetites and type 2 diabetes."
Seeley said PPAR-gamma is a system designed at all levels to help you prepare to eat more and gain weight opening up the possibility that food we eat that can activate PPAR-gamma might contribute to increasing rates of obesity.
"It tells your brain to eat more and it tells your fat tissue to add new fat cells to serve as repositories to store those extra calories."
The research appears as an advanced online publication in the journal Nature Medicine. ANI
