Researchers Reveal That the Sympathetic Nervous System, not White Blood Cells, is Critically Important in the Regulation of Energy Expenditure and Thermogenesis
A new study from the Icahn School of Medicine at Mount Sinai provides important insights into how the body regulates its production of heat, a process known as thermogenesis that is currently intensely studied as a target of diabetes and obesity treatment in humans.
While researchers had previously hypothesized that macrophages, a class of white blood cells, played a major role in thermogenesis, the new study suggests that the main driver of thermogenesis is the sympathetic nervous system, which is chiefly controlled by the brain. The results were published online today in Nature Medicine.
The Mount Sinai research team led by Christoph Buettner, MD, PhD, senior author of the study and Professor of Medicine (Endocrinology, Diabetes, and Bone Disease) at the Icahn School of Medicine at Mount Sinai, focused on catecholamines, hormones released by the sympathetic nervous system to activate brown fat tissue. Brown adipose tissue is a type of fat tissue that burns energy to produce heat and keep us warm. Catecholamines can also convert white fat tissue, the more familiar kind of fat tissue that stores lipids, into a tissue that resembles brown fat. The researchers tested whether macrophages could provide an alternative source of catecholamines, as had been proposed in recent years.
“Thermogenesis is a metabolic process that receives a lot of interest as a target of drugs that allow you to burn energy and hence reduce obesity and improve diabetes. It turns out that macrophages are not that important, as they are unable to make catecholamines, but clearly the brain through the sympathetic nervous system is,” says Dr. Buettner. “Therefore, it is very important to study the role of the brain and the sympathetic nervous system when it comes to understanding metabolism.”
The ability to generate heat is critical for the survival of warm-blooded animals, including humans, as it prevents death by hypothermia. “This evolutionary pressure shaped the biology of humans and that of other warm-blooded animals, and may in part explain why humans are susceptible to developing diabetes in the environment in which we live,” says Dr. Buettner.
According to Dr. Buettner, while a lot of effort has been invested in targeting the immune system to cure diabetes and insulin resistance, as of yet there are no anti-inflammatory drugs that have been shown to work well in humans with metabolic disease. “Our study suggests that perhaps the key to combating the devastating effects of diabetes and obesity in humans is to restore the control of thermogenesis and metabolism by the brain and the autonomic nervous system,” says Dr. Buettner.
This study was performed collaboratively between Mount Sinai and eight other institutions from around the world, most prominently with the group of Timo D. Müller, PhD, Institute for Diabetes and Obesity at the Helmholtz Center Munich in Germany.
This work was further supported by grant from the German Research Foundation DFG-TS226/1-1, DFG-TS226/3-1,SFB1123, Nutripathos Project ANR-15-CE14-0030, European Research Council ERC AdG HypoFlam no. 695054 (to M.H.T.); DFG He3260/8-1, the EU FP7 Network “DIABAT,” the EU ITN Network “TRAIN” 721531 (to S.H.); NIH R01AA023416, DK082724 and a career-development award from the American Diabetes Association (to C.B.); NIH R01DK099222 (to S.D.); NIH DK17844 (to S.C.W.); the Israeli Science Foundation and European Research Council (AdvERC grant 340345) (to S.J.) and the Swedish Research Council and the Knut and Alice Wallenberg Foundation (to J.N. and B.C.).
About the Mount Sinai Health System
The Mount Sinai Health System is New York City's largest integrated delivery system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The Health System includes approximately 7,480 primary and specialty care physicians; 11 joint-venture ambulatory surgery centers; more than 410 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools", aligned with a U.S. News & World Report's "Honor Roll" Hospital, No. 12 in the nation for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 18 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Gastroenterology/GI Surgery, Geriatrics, Nephrology, and Neurology/Neurosurgery, and in the top 50 in six other specialties in the 2018-2019 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 11th nationally for Ophthalmology and 44th for Ear, Nose, and Throat. Mount Sinai Beth Israel, Mount Sinai St. Luke's, Mount Sinai West, and South Nassau Communities Hospital are ranked regionally.