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An organelle’s role in appetite, weight gain

Medicine@Yale, 2014 - Mar Apr


Mitochondria, organelles that serve as the powerhouses of living cells, generate and maintain proper energy levels in complex organisms. But they do more than just generate energy.

A new School of Medicine study shows that the size and shape of mitochondria in specialized brain cells is key to controlling appetite and weight gain in mice. Analyzing AgRP neurons in mice, known to play a role in appetite, the team found that in a fasting state, the neurons had many small mitochondria. When the mice were fed high fat diets, the mitochondria fused together: they were fewer in number, but larger. To test whether these changes were integral to how AgRP functioned, the team blocked mitochondria from fusing in the AgRP neurons of some mice. The mice not only had impaired neuron signaling when they ate, but failed to gain weight on a high-fat diet.

The findings, reported September 25 in Cell, show a direct link between mitochondria changes and whole-body metabolism. “Mitochondra need to have ongoing dynamic plasticity in order to support neurons, which are necessary for appetite and for the maintenance of life,” said lead author Tamas L. Horvath, DVM, Ph.D., the Jean and David W. Wallace Professor of Biomedical Research and chair of the Section of Comparative Medicine.