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."
A drug that targets this mechanism would make fasting much easier.
Appetite-stimulating neurons get more mitochondria made in them. Those mitochondria produce more energy molecules that drive the appetite-stimulating neurons to send out more signals to produce a stronger desire to eat.
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."
Strong genetically driven mechanisms to make us eat are the product of selective pressures going back millions of years. Food shortages were a very common problem. Hence we have neural mechanisms that make us eat too much in an era of plenty. We need to develop biotechnologies that let us control our instincts for food.
|Share |||Randall Parker, 2007 January 16 09:47 PM Brain Appetite|