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Why TZDs Used to Treat Diabetes Also Increase Hunger

by U.S. Medicine

August 9, 2015

AUGUSTA, GA — Thiazolidinediones (TZDs) appear to activate sensors in brain cells diabetes patients, increasing hunger and causing users to gain more body fat, according to a new study.

The animal study, published recently in the Journal of Neuroscience, sought to find a new way to affect hunger in the brain and to help to explain why patients taking a specific class of drugs gain more body fat.1

Researchers from the Charlie Norwood VAMC and Georgia Regents University, both in Augusta, GA; Georgia State University in Atlanta and Oregon Health & Science University in Portland, found that sensors in the brain that detect free circulating energy and help use sugars are located on brain cells that control eating behavior.

This is important because many people with type II diabetes are taking antidiabetics which specifically activate these sensors, study authors point out.

The study found peroxisome proliferator-activated receptor &Upsih; (PPAR&Upsih;) sensors on hunger-stimulating cells, known as agouti-related protein (AgRP) cells, at the base of the brain in the hypothalamus. Activating these PPAR&Upsih; sensors triggers food hoarding, food intake and the production of more AgRP. When AgRP cells are activated, animals become immediately hungry.

These cells are so potent they will wake a rodent up from slumber to go eat, explained study author Johnny Garretson, a doctoral student in the Neuroscience Institute and Center for Obesity Reversal at Georgia State.

“People taking these TZDs are hungrier, and they do gain more weight. This may be areason why,” Garretson said. “When they’re taking these drugs, it’s activating these receptors, which we believe are controlling feeding through this mechanism that we found. We discovered that activating these receptors makes our rodent animal model eat more and store more food for later, while blocking these receptors makes them eat less and store less food for later, even after they’ve been food-deprived and they’re at their hungriest.”

1Garretson JT, Teubner BJW, Grove KL, Vazdarjanova, et. al. Peroxisome Proliferator-Activated Receptor Controls Ingestive Behavior, Agouti-Related Protein, and Neuropeptide Y mRNA in the Arcuate Hypothalamus. Journal of Neuroscience, 2015; 35 (11): 4571


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