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!
Building blocks for new medications: the University of Graz is seeking a technology partner
19.03.2019 | Karl-Franzens-Universität Graz
Scientists find new approach that shows promise for treating cystic fibrosis
14.03.2019 | NIH/National Heart, Lung and Blood Institute
The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.
A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...
Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.
"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...
New research group at the University of Jena combines theory and experiment to demonstrate for the first time certain physical processes in a quantum vacuum
For most people, a vacuum is an empty space. Quantum physics, on the other hand, assumes that even in this lowest-energy state, particles and antiparticles...
Physicists in the EPic Lab at University of Sussex make crucial development in global race to develop a portable atomic clock
Scientists in the Emergent Photonics Lab (EPic Lab) at the University of Sussex have made a breakthrough to a crucial element of an atomic clock - devices...
Every year earthquakes worldwide claim hundreds or even thousands of lives. Forewarning allows people to head for safety and a matter of seconds could spell...
11.03.2019 | Event News
01.03.2019 | Event News
28.02.2019 | Event News
19.03.2019 | Physics and Astronomy
19.03.2019 | Life Sciences
19.03.2019 | Physics and Astronomy