Hunger, Weight Gain Risk With These Diabetes Drugs - But Why?
A specific drug class for the treatment of type 2 diabetes has been linked to an increased risk of weight gain, and researchers have new clues as to how these medications may activate sensors in the brain that lead to increased hunger. The results of this study appear in The Journal of Neuroscience.
John T. Garretson, a doctoral student at George State University, and colleagues sought to investigate the mechanisms for the effects of peroxisome proliferator-activated receptor agonists (PPARs), known as the drug class thiazolidinediones (TZDs), on increased food intake and body/fat mass. Using animal models of Siberian hamsters and mice, the researchers discovered that activating the peroxisome proliferator-activated receptor gamma (PPARG) sensors triggered food hoarding, food intake, and the production of more hunger-stimulating agouti-related protein (AgRP) cells. The animals became immediately hungry when the AgRP cells were activated; when activated, the cells can wake up a rodent from sleep to go eat. Blocking the receptors led to the animals eating less and storing less food for later, even after they were deprived of food and at their hungriest.
The authors believe that this mechanism may help to explain the increased hunger and weight gain associated with TZD treatment in patients with type 2 diabetes. These findings may help to guide future therapies for type 2 diabetes that do not trigger these sensors.
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