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.
The role 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 Medicine in an accompanying preview article. Researchers had thought that decreased levels of the fat-produced hormone leptin alone signaled the hypothalamus that fat levels have fallen, leading hypothalamic neurons to activate a program, including hunger, to preserve energy and restore fat levels, he said.
Now, "a series of studies, including those reported in this issue of Cell Metabolism by [Diano and colleagues] have elegantly demonstrated that hypothalamic responses to food deprivation involve at least three hormones, two cell types, and an unexpected interlocutor, uncoupling protein 2."
Erin Doonan | EurekAlert!
Nanoparticles as a Solution against Antibiotic Resistance?
15.12.2017 | Friedrich-Schiller-Universität Jena
Plasmonic biosensors enable development of new easy-to-use health tests
14.12.2017 | Aalto University
A study carried out by an international team of researchers and published in the journal Physical Review X shows that ion-trap technologies available today are suitable for building large-scale quantum computers. The scientists introduce trapped-ion quantum error correction protocols that detect and correct processing errors.
In order to reach their full potential, today’s quantum computer prototypes have to meet specific criteria: First, they have to be made bigger, which means...
Since 2016, German and Spanish researchers, among them scientists from the University of Göttingen, have been hunting for exoplanets with the “Carmenes”...
DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.
Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
18.12.2017 | Information Technology
18.12.2017 | Physics and Astronomy
18.12.2017 | Agricultural and Forestry Science