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T2DM medication

Study: Why drugs for T2DM increase weight gain

T2DM medication increases hunger, causing people taking this drug to gain more body fat,

Medication used to treat patients with type II diabetes activates sensors on brain cells that increase hunger, causing people taking this drug to gain more body fat, according to researchers at Georgia State University, Oregon Health and Science University, Georgia Regents University and Charlie Norwood Veterans Administration Medical Center.

The study, ‘Peroxisome Proliferator-Activated Receptor γ Controls Ingestive Behavior, Agouti-Related Protein, and Neuropeptide Y mRNA in the Arcuate Hypothalamus.’ published in The Journal of Neuroscience, describes a new way to affect hunger in the brain and helps to explain why people taking a class of drugs for type II diabetes gain more body fat.

The research team found that sensors in the brain that detect free circulating energy and help use sugars are located on brain cells that control eating behaviour. This is important because many people with type II diabetes take thiazolidinediones (TZDs) antidiabetics, which specifically activate these sensors, said Johnny Garretson, study author and doctoral student in the Neuroscience Institute and Center for Obesity Reversal at Georgia State.

The study found peroxisome proliferator-activated receptor receptor ϒ (PPARϒ) sensors on hunger-stimulating cells, known as agouti-related protein (AgRP) cells, at the base of the brain in the hypothalamus. Activating these PPARϒ 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, Garretson said.

"People taking these TZDs are hungrier, and they do gain more weight. This may be a reason 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."

The research team includes Dr Timothy Bartness, director of the Center for Obesity Reversal at Georgia State; Johnny Garretson and Drs Brett JW Teubner and Vitaly Ryu of Georgia State; Dr Kevin L Grove of Oregon Health and Science University; and Dr Almira Vazdarjanova of Georgia Regents. The study was funded by the National Institutes of Health and National Science Foundation.

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