Nicknamed the “longevity” protein because of its apparent role in mediating the effects of dietary restriction on life span, SIRT1 has been studied as a potential target for anti-aging drugs. Prior research also has shown that this metabolic sensor protein in peripheral tissues plays an important role in regulating metabolism, but its physiological relevance in brain neurons remained unclear.
“This is the first study to show that SIRT1 in hypothalamic neurons, specifically POMC neurons, is required for preventing diet-induced obesity and maintaining normal body weight,” said Dr. Roberto Coppari, assistant professor of internal medicine at UT Southwestern and senior author of the mouse study, available online and in the July 7 issue of Cell Metabolism.
POMC, or pro-opiomelanocortin, neurons are found in the hypothalamus region of the brain and are known to play an important role in suppressing appetite and inducing weight loss. There are about 3,000 POMC neurons in a mouse brain.
The researchers genetically engineered mice to lack SIRT1 only in these specific hypothalamic neurons. They found that when fed a high-calorie diet, the mice lacking SIRT1 in POMC neurons gained more weight and were generally more susceptible to diet-induced obesity than those with the metabolic sensor protein intact.
The mutant mice also had almost twice as much abdominal fat and more of the hormone leptin than those mice with their SIRT1 intact, despite the fact that all the mice maintained the same food intake and movement levels.
“We found that SIRT1 must be present in POMC neurons in order for the hormone leptin to properly engage its receptors in these neurons. Without SIRT1, leptin sensing is altered and the animals gain more fat mass when fed a high-calorie diet,” Dr. Coppari said.
In addition, the researchers found that SIRT1 must be present in POMC neurons for leptin to stimulate the remodeling of white adipose tissue into brown fat tissue, which “burns” fat to generate heat. White adipocytes primarily store fat.
“When SIRT1 is present in POMC neurons, the neurons properly convey a signal from leptin to the white perigonadal fat, which is designed to store energy. This signal is needed for the fat to undergo a remodeling process and expand the brown fat cells component as a protective measure against obesity,” Dr. Coppari said. “If you don’t have these kinds of defense mechanisms, you likely become hypersensitive to diet-induced obesity. A primary defect in SIRT1 in POMC neurons might be present in some individuals who are more prone to develop obesity when constantly exposed to an abundance of high-fat, high-calorie foods.”
Dr. Coppari said the idea of a drug that selectively could target neurons controlling specific fat depots – and that could trigger the remodeling of white fat into brown fat – has high potential.
“The drawback to harnessing adrenergic receptors to make more brown adipocytes, as a lot of people are thinking about doing, is that it puts a lot of pressure on the cardiovascular system,” he said. “However, the idea of having a drug that could selectively affect specific hypothalamic neurons that then control specific branches of the sympathetic nervous system suggests that one could avoid acting on unwanted cells but selectively on those able to burn calories such as brown adipocytes.
“We could control the remodeling of a particular fat depot into brown, which would then be more likely to cause weight loss without increasing the risk of cardiovascular problems,” he said.
The next step, Dr. Coppari said, is to determine whether SIRT1 is mediating other signaling pathways in the brain that in addition to regulating body weight are key for normal glucose balance.
Other UT Southwestern researchers involved in the study were Dr. Giorgio Ramadori, lead author and postdoctoral researcher in internal medicine; Dr. Teppei Fujikawa, postdoctoral researcher in internal medicine; Drs. Makoto Fukuda and Claudia Vianna, instructors of internal medicine; Jason Anderson, student research assistant in internal medicine; and Dr. Mario Perello, former postdoctoral researcher in internal medicine.
Researchers from the University of Iowa, Harvard Medical School and Brown University/Rhode Island Hospital also contributed to the study, which was funded by the National Institutes of Health and the American Heart Association.
Kristen Holland Shear | Newswise Science News
Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania
The strange double life of Dab2
10.01.2017 | University of Miami Miller School of Medicine
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration
"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...
Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.
Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
16.01.2017 | Power and Electrical Engineering
16.01.2017 | Information Technology
16.01.2017 | Power and Electrical Engineering