PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Cell nucleus protein in brown fat cells governs daily control of body temperature

Biorhythm of brown fat has implications for combating obesity, associated diabetes and heart disease, finds an interdisciplinary team from Penn Medicine

2013-10-28
(Press-News.org) Contact information: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Cell nucleus protein in brown fat cells governs daily control of body temperature Biorhythm of brown fat has implications for combating obesity, associated diabetes and heart disease, finds an interdisciplinary team from Penn Medicine

PHILADELPHIA - For nearly 300 years, investigators have known that body temperature follows a circadian, or 24-hour, rhythm, with a peak during the day and a low at night. The benefit of this control during evolution may have been to allow conservation of energy while sleeping because keeping body temperature above the surrounding temperature requires heat production from metabolic processes inside the body. But, it is also critical to be able to adapt to changes in ambient temperature, regardless of the time of day.

However, the mechanism responsible for coordinating daily body temperature rhythm and adaptability to environmental challenges is unknown. Now, the laboratory of Mitchell A. Lazar, MD, PhD, director of the Institute for Diabetes, Obesity, and Metabolism at the Perelman School of Medicine, University of Pennsylvania explains in Nature how body temperature rhythms are synchronized while maintaining the ability to adapt to changes in environmental temperature no matter the time of day or night.

"Food is plentiful in our present day society, and for most people there is unlikely to be an advantage of saving calories at night", says Lazar. "If this same mechanism exists in people, and we can target it safely, we could have a new way to combat obesity and its associated conditions such as diabetes and heart disease."

Lazar's team, including lead author Zachary Gerhart-Hines, Ph.D., found that the ability of mice to withstand a cold-temperature challenge was greater at 5:00 AM, when the mice are awake, compared to 5:00 PM when they are normally sleeping. This previously unrecognized circadian susceptibility to cold was found to be controlled by a protein called Rev-erb alpha, which is a molecular component of the body's biological clock mechanism.

Indeed, mice engineered to lack the Rev-erb alpha protein had similar cold tolerance throughout the 24-hour day and also lost the physiological circadian rhythm of body temperature. The all-Penn team of authors represents a broad set expertise, including those who study brown fat physiology, radiology for PET scans of experimental mice, and basic physiologists who ruled out shivering as an explaining mechanism for the findings.

The Penn team concluded that Rev-erb alpha acts as a focal point for dialing body temperature up and down and is required for establishing and maintaining fundamental, body-temperature rhythm, while affording adaptability to respond to environmental demands of unpredictable changes in ambient temperatures.

Role of Brown Fat

Rev-erb alpha's effects were produced mainly by circadian regulation in brown adipose tissue, commonly called brown fat, the body's furnace. Brown fat cells, as opposed to white fat cells, make heat for the body and are thought to have evolved to help mammals cope with the cold. But, their role in generating warmth might also be applied to coping with obesity and diabetes. Brown fat cells are thought to counteract obesity by burning off excess energy stored in lipid, but white fat cells store energy. Indeed, brown fat cells contain many smaller droplets of lipids and the most mitochondria (containing pigmented cytochromes that bind iron) of any cell type, which make them brown. Mitochondria are the cells' energy factories in the form of the molecule ATP.

The mice that are exposed to cold fare dramatically better -- their body temperature goes down less -- early in the morning when Rev-erb alpha is barely present compared to the late afternoon, when Rev-erb alpha is abundant. Deletion of the gene Rev-erbα markedly improves cold tolerance at 5 PM, indicating that tolerance to cold is related to lower levels of the Rev-erb alpha protein.

More specifically, turning on the uncoupling protein 1 (UCP1) by cold temperatures is preceded by rapid downregulation of Rev-erbα in brown fat. Rev-erb alpha represses UCP1 in a brown fat cell-autonomous manner – the effect is direct in the brown fat, rather than operating through the nervous system. Brown fat UCP1 levels are high in mice without Rev-erbα even when ambient temperatures remain constant. Genetic loss of Rev-erbα also abolishes normal rhythms of body temperature and brown-fat activity.

The recent discovery of brown fat tissue in humans suggests that the same mechanism could underlie the daily fluctuations in body temperature in people. Although the lowering of body temperature may have had a survival advantage during evolution, by preserving energy stores when food was scarce, in modern times, lower body temperatures, and therefore lower metabolism and reduced burning of stored fats while sleeping, could contribute to the obesity problem. Knowledge of the mechanism that lowers body temperature at night may provide a way to burn calories while people are sleeping.



INFORMATION:

This work was supported by the National Institute of Diabetes, Digestive, and Kidney Diseases (DK45586; F-32 DK095563) and by the JPB Foundation. Other co-authors include Dan Feng, Matthew Emmett, Logan Everett, Emanuele Loro, Erika Briggs, Anne Bugge, Catherine Hou, Christine Ferrara, Patrick Seale, Daniel Pryma, and Tejvir Khurana, all from Penn.

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 16 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $398 million awarded in the 2012 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2012, Penn Medicine provided $827 million to benefit our community.



ELSE PRESS RELEASES FROM THIS DATE:

International group finds 11 new Alzheimer's genes to target for drug discovery

2013-10-28
International group finds 11 new Alzheimer's genes to target for drug discovery Global collaboration including Penn Medicine experts yields fresh look at role of immune system in Alzheimer's PHILADELPHIA - The largest international Alzheimer's ...

Brief exposure to performance-enhancing drugs may be permanently 'remembered' by muscles

2013-10-28
Brief exposure to performance-enhancing drugs may be permanently 'remembered' by muscles Brief exposure to anabolic steroids may have long lasting, possibly permanent, performance-enhancing effects, shows a study published today [28 October] in The Journal of Physiology. Previously, ...

Smart neurons: Single neuronal dendrites can perform computations

2013-10-28
Smart neurons: Single neuronal dendrites can perform computations When you look at the hands of a clock or the streets on a map, your brain is effortlessly performing computations that tell you about the orientation of these objects. New research by UCL scientists ...

New material for quantum computing discovered out of the blue

2013-10-28
New material for quantum computing discovered out of the blue A common blue pigment used in the £5 note could have an important role to play in the development of a quantum computer, according to a paper published today in the journal Nature. The pigment, ...

11 new genetic susceptibility factors for AD discovered through the largest study

2013-10-28
11 new genetic susceptibility factors for AD discovered through the largest study Findings a major breakthrough in the understanding of Alzheimer's disease (Boston)-- The largest international study ever conducted on Alzheimer's disease (AD), the I-GAP ...

NIH-supported study identifies 11 new Alzheimer's disease risk genes

2013-10-28
NIH-supported study identifies 11 new Alzheimer's disease risk genes International groups join forces to find elusive gene variants in largest-ever sample set An international group of researchers has identified 11 new genes that offer important new insights ...

UNC neuroscientists discover new 'mini-neural computer' in the brain

2013-10-28
UNC neuroscientists discover new 'mini-neural computer' in the brain CHAPEL HILL, N.C. – Dendrites, the branch-like projections of neurons, were once thought to be passive wiring in the brain. But now researchers at the University ...

International collaboration finds 11 new Alzheimer's genes to target for drug discovery

2013-10-28
International collaboration finds 11 new Alzheimer's genes to target for drug discovery Study yields fresh look at role of immune system in Alzheimer's MIAMI -- University of Miami Miller School of Medicine researchers played a key role in the largest international ...

Study with totally blind people shows how light helps activate the brain

2013-10-28
Study with totally blind people shows how light helps activate the brain This news release is available in French. Light enhances brain activity during a cognitive task even in some people who are totally blind, according to a study conducted ...

Bird buffet requires surveillance

2013-10-28
Bird buffet requires surveillance Sandpipers exhibit different feeding behavior depending on position in group The behaviour of semipalmated sandpipers (Calidris pusilla) feeding during low tide in the Bay of Fundy, New Brunswick, surprised Guy ...

LAST 30 PRESS RELEASES:

KAIST Develops Retinal Therapy to Restore Lost Vision​

Adipocyte-hepatocyte signaling mechanism uncovered in endoplasmic reticulum stress response

Mammals were adapting from life in the trees to living on the ground before dinosaur-killing asteroid

Low LDL cholesterol levels linked to reduced risk of dementia

Thickening of the eye’s retina associated with greater risk and severity of postoperative delirium in older patients

Almost one in ten people surveyed report having been harmed by the NHS in the last three years

Enhancing light control with complex frequency excitations

New research finds novel drug target for acute myeloid leukemia, bringing hope for cancer patients

New insight into factors associated with a common disease among dogs and humans

Illuminating single atoms for sustainable propylene production

New study finds Rocky Mountain snow contamination

Study examines lactation in critically ill patients

UVA Engineering Dean Jennifer West earns AIMBE’s 2025 Pierre Galletti Award

Doubling down on metasurfaces

New Cedars-Sinai study shows how specialized diet can improve gut disorders

Making moves and hitting the breaks: Owl journeys surprise researchers in western Montana

PKU Scientists simulate the origin and evolution of the North Atlantic Oscillation

ICRAFT breakthrough: Unlocking A20’s dual role in cancer immunotherapy

How VR technology is changing the game for Alzheimer’s disease

A borrowed bacterial gene allowed some marine diatoms to live on a seaweed diet

Balance between two competing nerve proteins deters symptoms of autism in mice

Use of antifungals in agriculture may increase resistance in an infectious yeast

Awareness grows of cancer risk from alcohol consumption, survey finds

The experts that can outsmart optical illusions

Pregnancy may reduce long COVID risk

Scientists uncover novel immune mechanism in wheat tandem kinase

Three University of Virginia Engineering faculty elected as AAAS Fellows

Unintentional drug overdoses take a toll across the U.S. unequally, study finds

A step toward plant-based gelatin

ECMWF unveils groundbreaking ML tool for enhanced fire prediction

[Press-News.org] Cell nucleus protein in brown fat cells governs daily control of body temperature
Biorhythm of brown fat has implications for combating obesity, associated diabetes and heart disease, finds an interdisciplinary team from Penn Medicine