A hormone seen as a popular target to develop weight-loss drugs works by directly targeting the brain and triggering previously unknown activity in the nervous system, UT Southwestern Medical Center obesity researchers have found.
The fibroblast growth factor 21 (FGF21) hormone has been a key target for developing weight-loss drugs because the protein increases energy expenditure, causing the body to burn calories. But how the hormone worked wasn't known until now.
This image shows Dr. David Mangelsdorf and Dr. Steven Kliewer.
Credit: UT Southwestern
UT Southwestern researchers tracking the hormone discovered that FGF21 acts directly on the brain, activating another hormone called corticotropin-releasing factor (CRF). CRF then stimulates the nervous system, activating brown adipose tissue, which generates body heat by burning fat.
"FGF21 is well known for playing a role in weight loss and we had previously shown that the hormone can act directly on the brain in mice to influence functions like reproduction. In the new study we show that FGF21 also acts directly on the brain to regulate obesity," said Dr. Steven Kliewer, Professor of Molecular Biology and Pharmacology, who holds the Nancy B. and Jake L. Hamon Distinguished Chair in Basic Cancer Research at UT Southwestern.
Specifically, researchers found that the FGF21-CRF pathway activates a part of the nervous system that controls various involuntary body functions, called the sympathetic nervous system, to signal to brown fat. Brown fat is often considered the "good" fat that actually burns energy by generating heat — called thermogenesis — to protect from the cold. Once brown fat receives a "weight loss" signal, the tissue burns fat.
The findings, published in the journal Cell Metabolism, are important to ongoing efforts to understand obesity at a molecular level and thus better respond to the obesity epidemic.
More than one-third of U.S. adults — about 35 percent — are obese, according to the Centers for Disease Control, with obesity-related conditions such as heart disease, stroke, type 2 diabetes, and certain types of cancer among the leading causes of preventable disease. Obesity also takes a dramatic financial toll, costing an estimated $150 billion annually or, on an individual basis, an additional $1,429 in higher medical costs than those of normal weight.
"We have made great strides in understanding obesity in recent years," said senior author Dr. David Mangelsdorf, Chairman of Pharmacology, a Howard Hughes Medical Institute investigator, and holder of the Distinguished Chair in Pharmacology, and the Raymond and Ellen Willie Distinguished Chair in Molecular Neuropharmacology in Honor of Harold B. Crasilneck, Ph.D. "What this research shows is that the central nervous system must be considered when looking for weight loss treatments."
Dr. Mangelsdorf and Dr. Kliewer are members of UT Southwestern's Taskforce for Obesity Research (TORS), composed of investigators from diverse disciplines who examine the behavioral, metabolic, and cellular mechanisms that cause obesity and metabolic syndrome.
Their primary goal is to elucidate how the brain regulates food intake and energy expenditure, and to determine how dysregulation of glucose and lipid metabolism in the liver causes the metabolic syndrome. The long-term goal is to develop more directed approaches to prevent obesity and treat related metabolic complications. Dr. Mangelsdorf and Dr. Kliewer are part of the team studying the molecular biology of energy metabolism.
Other UT Southwestern researchers in this latest study include postdoctoral researchers Dr. Bryn Owen, Dr. Xunshan Ding, Dr. Katie Colbert-Coate, and Dr. Angie Bookout.
The study was supported by the National Institutes of Health, the Robert A. Welch Foundation, the American Heart Association, and the Howard Hughes Medical Institute.
About UT Southwestern Medical Center
UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to about 92,000 hospitalized patients and oversee approximately 2.1 million outpatient visits a year.
Russell Rian | Eurek Alert!
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...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
27.04.2017 | Life Sciences
27.04.2017 | Physics and Astronomy
27.04.2017 | Earth Sciences