Mitochondria, key to obesity

New Yale research on how the brain processes fatty diets may help scientists develop better treatments for obesity.

In a study that appeared on the cover of the journal Cell on Sept. 26, Yale School of Medicine researchers showed that when mice switched from a fasted to overfed state, the mitochondria of neurons in the part of the brain responsible for controlling appetite changed in response to the new diet. Individual differences in how mitochondria — the cellular structures responsible for the energy production — in neurons respond to the caloric intake control influenced how the body deposits fat, Yale lead author and research scientist Marcelo de Oliveira Dietrich said.

“The implications are multiple,” Dietrich said. “The most appealing is that understanding the cellular events behind the development of diseases like obesity allows us to better target treatments and develop therapies to treat these conditions.”

To carry out the study, researchers started feeding mice a high calorie diet to observe changes in mitochondria. When researchers then impaired the mitochondrial response to diet changes, even the mice with high calorie diets did not gain weight.

A previous study had shown that mitochondrial adaptations were key to regulating brain responses to diet, motivating questions on how neurons are able to fire at different rate as metabolic conditions change. This study sets a basis for providing a wider discussion of the interaction of cellular, neural and molecular mechanisms for treating diseases such as obesity, Dietrich said.

This research also shows that there are better options to fight obesity than current ones that kill off cells that have been evolutionally significant in promoting appetite, Dietrich said. Understanding the function of neuronal mitochondria in disease may help researchers develop more targeted treatments for obesity in the future, he added.

“This is very important, because most — if not all — the treatments for chronic disorders are developed against pathways that target the whole individual, and not single cell populations,” Dietrich added in an email to the News. “We provide experimental evidence in animal models that such drug design will surely lead to side effects not desired.”

Future directions for research include observing whether changes in mitochondrial dynamics are present in other cells and how these mitochondrial changes affect disease, senior author and professor of comparative medicine Tamas Horvath said.

The study was funded by the National Institute of Health, American Diabetes Association, The Helmholtz Society and the Conselho Nacional de Desenvolvimento Científico e Tecnológico.

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