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Study tracks brain’s trigger for overeating high-fat food

Sep. 24, 2015, 10:27 AM

Disruptions in a specific signaling pathway in the brain can cause overeating of high-fat food, researchers at Vanderbilt University have found.

The study in mice was published this week in the new open access journal Heliyon. It has implications for understanding and potentially correcting defects in the regulation of food intake that may lead to obesity in humans.

“Our findings reveal a system designed to control eating of rewarding foods that are high in fat and possibly sugar,” one of the authors, Aurelio Galli, Ph.D., told the journal. “This system can be hijacked by the very foods it is designed to control.”

Galli and co-authors Olga Dadalko and Kevin Niswender, M.D., Ph.D., focused on the mammalian target of rapamycin complex 2 (TORC2), a multiprotein complex that is involved in insulin signaling in various circuits in the brain.

By genetically “knocking out” part of the TORC2 complex in the catecholamine system, the researchers found that they could induce exaggerated hyperphasia (excessive appetite) in the presence of high-fat foods. The catecholamine system includes dopamine, a neurotransmitter involved in reward and appetite.

These findings support a model in which TORC2 signaling within this system normally constrains consumption of a high-fat diet in order to balance caloric intake and expenditure. Impaired TORC2 signaling leads to abnormal dopamine neurotransmission and overrides the brakes on high-fat food consumption.

Eating a high-fat or high-carbohydrate diet appears to cause changes in areas of the brain involved in controlling eating, explained Galli, professor of Molecular Physiology and Biophysics and of Psychiatry.

“Our study shows that when specific signaling in these areas of the brain is disrupted, it leads to a vicious cycle of increasing, escalating high-fat diet intake,” he told the journal.

The researchers now plan to restore normal TORC2 signaling in obese mice to see if that reins in over-eating.

Dadalko, the study’s first author, is a graduate student in Galli’s lab. Niswender is associate professor of Medicine and of Molecular Physiology and Biophysics. The study was supported in part by National Institutes of Health grants DA038058 and DK085712.

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