Obesity, diabetes, and the brain

It’s an exaggeration to say that diabetes and obesity are all in your head. But a Yale research team has made two new discoveries about the brain’s role in developing these conditions—and potentially in treating them.

The study that’s getting more attention, not surprisingly, is the one in which mice ate a high-fat, high-sugar diet without gaining weight. “Preventing weight gain, obesity, and ultimately diabetes could be as simple as keeping a nuclear receptor from being activated in a small part of the brain,” says a YaleNews release.

A second study, focusing specifically on diabetes, might bring help not only for people with obesity-related type 2 diabetes, but also for patients with type 1 diabetes.

The lead author of both studies is Sabrina Diano, professor in the School of Medicine’s departments of Obstetrics, Gynecology & Reproductive Sciences, Comparative Medicine, and Neurobiology.

In the obesity study, published in the Journal of Clinical Investigation, researchers blocked the effects of a nuclear receptor called PPARgamma in the brain cells of mice. The result: “These animals ate fat and sugar, and did not gain weight, while their control littermates did,” Diano says.

The finding could boost the effectiveness of a class of diabetes drugs called thiazolidinedione (TZD), YaleNews says. TZD targets PPARgamma to lower blood glucose levels, but it also causes patients to gain weight. Diano proposes targeting “peripheral PPARgamma” with a TZD formulation that doesn’t penetrate the brain, in hopes of gaining the glucose reduction without the weight gain.

The diabetes study, published in the Proceedings of the National Academies of Sciences, pinpoints an enzyme that helps neurons detect glucose in the blood. Once they detect the glucose, the neurons signal the pancreas to produce insulin, which lowers the blood-sugar level.

When the researchers engineered mice with low levels of the enzyme, prolyl endopeptidase (PREP), “the neurons were no longer sensitive to increased glucose levels and could not control the release of insulin from the pancreas, and the mice developed diabetes,” Diano says.

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The Yale Alumni Magazine is published by Yale Alumni Publications Inc., an alumni-based nonprofit that is not run by Yale University. Its content does not necessarily reflect the views of the university administration.