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How appetite-stimulating brain cells work overtime during fasting

ole of the related protein, UCP2, which is present at high levels in the hypothalamic arcuate nucleus--considered to be the key brain site that responds to changes in peripheral tissue metabolism--had remained less clear. However, scientists did know that that portion of the brain harbors thyroid hormone receptors and has the capacity for local production of T3.

Now, the researchers found that support cells in the hypothalamus producing an enzyme that catalyzes active thyroid hormone production are side by side with appetite-stimulating neurons that express UCP2. In mice that were fasted for 24 hours, the arcuate nucleus showed an increase in the "DII" enzyme's activity and local thyroid production, in parallel with increased UCP2 activity.

This fasting-induced, T3-mediated UCP2 activation resulted in mitochondrial proliferation in the neurons, an event that was critical for the brain cells' increased excitability and consequent rebound feeding by the animals following food deprivation.

"Our results indicate that this mechanism is critical in sustaining an increased firing rate in these [hunger-stimulating] cells so that appetite remains elevated during fasting," Diano's group concluded. "Overall, our study provides strong evidence for an interplay between local T3 production and UCP2 during fasting and reveals a central thermogenic-like mechanism in the regulation of food intake."

While it is as yet unproven, the rise in UCP2 in the brain likely also causes changes in temperature in the same way that UCP1 does in brown fat, Diano said.

"It's possible that heat may act like a neurotransmitter of a sort," Diano said. Neurotransmitters are chemical messengers that relay signals to and from neurons. "Changes in temperature could have a strong effect on brain function."

The findings emphasize the complexity of the feeding circuitry, which once "seemed so simple," wrote Charles Mobbs of Mount Sinai School of M
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Source:Cell Press


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