Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes

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2012-03-01

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Bordicchia, Marica
Liu, Dianxin
Amri, Ez-Zoubir
Ailhaud, Gerard
Dessì-Fulgheri, Paolo
Zhang, Chaoying
Takahashi, Nobuyuki
Sarzani, Riccardo
Collins, Sheila

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10.1172/JCI59701

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Bordicchia, Marica, Dianxin Liu, Ez-Zoubir Amri, Gerard Ailhaud, Paolo Dessì-Fulgheri, Chaoying Zhang, Nobuyuki Takahashi, Riccardo Sarzani, et al. (2012). Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. Journal of Clinical Investigation, 122(3). pp. 1022–1036. 10.1172/JCI59701 Retrieved from https://hdl.handle.net/10161/11959.

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Collins

Sheila Collins

Adjunct Associate Professor in Psychiatry and Behavioral Sciences

Research Focus
One only has to open the newspaper or turn on the radio to hear about the epidemic of obesity in America. Not only does obesity exact a heavy toll on the population's health, but the medical costs associated with obesity, especially those related to treatment for type 2 diabetes and cardiovascular disease, are astronomical.

Our laboratory is interested in the biochemical mechanisms that regulate body weight. Until the mid-1990s, adipose tissue had been largely considered to be an inert storage depot for excess metabolic fuel. In the ensuing years, there has been a deeper appreciation that a fairly large number of cytokines and growth factors are secreted from adipose tissue and may play significant roles in insulin resistance and cell differentiation and growth.

Accumulation of excess calories as triglycerides in adipose tissue is largely driven by insulin, and subsequent access to this stored fuel is gated by the catecholamine to stimulate lipolysis. Activation of the adrenaline receptors, specifically the members of the beta-adrenergic receptor (beta-AR) family, are a major stimulus for the hydrolysis and release of stored lipids. There are three known beta-AR subtypes, one of which is expressed predominantly in the adipocyte: the beta3-AR. Our lab has been deciphering how the beta-ARs on fat cells are regulated and how their structural features dictate their signal transduction properties, including a process called nonshivering thermogenesis, in brown fat. Brown fat cells are specialized cells rich in mitochondria and defined by their ability to express the mitochondrial uncoupling protein UCP1, which allows the dissipation of the proton gradient in the inner mitochondrial membrane to yield heat at the expense of ATP production. Although known to exist in newborns humans, it was largely considered to be absent from adult humans. It is now understood that this assumption is incorrect and once again opens the opportunity to consider brown adipocytes as a potential means for improving energy expenditure and the ‘burning’ of calories as heat instead of storing them as fat.

We also study the cardiac natriuretic peptides ANP and BNP, which also can stimulate lipolysis by a parallel set of receptors, also increase the amount and activity of brown adipocytes, and we are investigating the regulation of this system, including in human subjects.  

These discoveries, as well as the realization that a host of biochemical and environmental factors contribute to the obesity epidemic, mark a new era in understanding how organ systems communicate their energy demands and reserves to regulate body weight.

Biography
Dr. Collins received her B.S., degree in Zoology from the University of Massachusetts at Amherst, after which she was a research technician at the Mass.General Hospital (Boston) and at the California Institute of Technology in Pasadena CA. She received her doctorate in biochemistry and drug metabolism from the Massachusetts Institute of Technology with Dr. Michael Marletta, and conducted postdoctoral research in the lab of Dr. Robert Lefkowitz at Duke University. Dr. Collins continued her research career at Duke University Medical Center by joining the faculty, being awarded tenure.  She was then a Professor of Integrative Metabolism at the Sanford BurnhamPrebys Medical Discovery Institute in Orlando, FL (home base La Jolla CA). She is currently Professor of Cardiovascular Medicine at Vanderbilt University Medical Center.  Dr. Collins has served on numerous review committees and advisory panels for the National Institutes of Health, the American Diabetes Association, and has been an organizer of many national and international scientific meetings.


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