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!
Millions through license revenues
27.04.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn
New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences