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How appetite-stimulating brain cells work overtime during fasting

During periods of fasting, brain cells responsible for stimulating the appetite make sure that you stay hungry. Now, a new study of mice reported in the January issue of the journal Cell Metabolism, published by Cell Press, reveals the complex series of molecular events that keep those neurons active.

The researchers revealed a link between active thyroid hormone in the brain and increases in an "uncoupling" protein (UCP2) that boosts the number of power-generating mitochondria in neurons that drive hunger. The increase in mitochondria, in turn, allows the brain's hunger center to remain active when periods of food scarcity result in a "negative energy balance," said Sabrina Diano of Yale University School of Medicine, who led the study.

Indeed, the researchers found, animals lacking either UCP2 or an enzyme that stimulates thyroid hormone's production ate less than normal after a period of food deprivation.

"This shows the key importance of UCP in the brain and its effect on neuronal activity," Diano said. "It's how neurons 'learn' that food is missing, and it keeps them ready to eat when food is introduced."

The mechanism involved is very similar to the one that regulates core body temperature in peripheral body tissues, Diano added.

Thyroid hormones are known to play major roles during development as well as in adulthood, the researchers said. In adults, the thyroid gland is essential to regulating metabolism. Previous studies had also established a key physiological role for the active thyroid hormone, triiodothyronine (T3), in the regulation of body temperature by heat-generating brown fat.

The molecular underpinning of heat production, or thermogenesis, in brown fat is the activation of mitochondrial uncoupling protein 1 (UCP1) by T3, the researchers said. The UCP1 activation, which is controlled by the sympathetic nervous system, also leads to an increase in the number of mitochondria.

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Source:Cell Press


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