Scientists identify culprit in obesity-associated high blood pressure

Researchers describe key mechanism responsible for brain's regulation of obesity-associated disease

2013-01-31

(Press-News.org) Obesity and its related conditions such as type 2 diabetes, cardiovascular disease and stroke are among the most challenging of today's healthcare concerns.

Together, they constitute the biggest killer in western society. New findings, published in Cell, have identified a target that could hold the key to developing safe therapies to treat obesity and its associated conditions.

Although recent research has begun to unravel some of the pathways that control how information is processed by our nervous system regulating body weight and cardiovascular function, the exact mechanisms through which signals are sensed by the brain and translated into co-ordinated metabolic and cardiovascular responses remain unclear.

A University of Bristol team, with funding from the British Heart Foundation (BHF), has now identified that a target found to be critical in the brain's regulation of body weight, is also crucially involved in the development of obesity-associated conditions. Researchers describe the mechanism behind a key molecule, known as melanocortin-4-receptor (MC4R), whose mutation or loss in both human and animal models has shown to cause severe obesity with type 2 diabetes.

While previous studies have shown that small activators of the molecule, which increase MC4R activity, have the desirable effect of reducing food intake and insulin secretion from the pancreas (important to suppress the development of type 2 diabetes), it is not clear how, at the same time, they trigger the undesirable effect of increasing blood pressure.

The team has now identified a mechanism for MC4R-mediated regulation of the activity of the autonomic nervous system to maintain appropriate blood pressure and insulin levels. The autonomic nervous system, which regulates internal organs and processes that are not under our control, is split into the parasympathetic and sympathetic nervous system, commonly exerting opposing influences on the structures they supply with nerves.

Researchers demonstrated that the activation of the MC4R inhibits parasympathetic neurons in the brain stem area of the central nervous system (CNS), while activating sympathetic neurons in the spinal cord. The team further demonstrates, in genetically-modified mouse models of human loss of MC4R function, that MC4Rs in these CNS areas are to blame for the development of obesity-induced increases in blood pressure.

They also report that MC4Rs in these CNS areas are pivotal in maintaining appropriate insulin levels to stave off type 2 diabetes. Thus, by carefully balancing positive and negative forces on the autonomic nervous system, the MC4R maintains equilibrium of appropriate blood pressure and insulin levels. This is independent of the MC4R's role in the regulation of food intake elsewhere in the CNS.

MC4R is a target of intense pharmaceutical interest and the data from this research helps in our understanding of the CNS mechanisms regulating homeostatic body weight, blood pressure and insulin levels through a distributed network of MC4Rs. These findings may facilitate the development of appropriate, safe therapies to treat obesity and its associated conditions.

Dr Nina Balthasar, one of the study's lead authors and a researcher in the University's School of Physiology and Pharmacology, said: "Obesity is a major risk factor for cardiovascular disease with recent statistics showing that obese adults are three to four times more likely to develop high blood pressure.

"In order to curb the escalating incidence of obesity and obesity-related diseases, a primary prevention goal must be to understand the physiological processes underlying our vulnerability to weight gain — knowledge that is central to the development of novel, effective therapies.

Our data illustrate the complexity of the CNS pathways governing the body's metabolic balance and highlight the challenges ahead for the development of safe therapies. "

Dr Shannon Amoils, Research Advisor at the BHF, which part-funded the study, added: "This research increases our understanding of how the nervous system affects our metabolism, and the development of high blood pressure due to obesity. With further knowledge of this complex area we hope scientists will be able to find safe and effective ways of treating obesity-related heart and circulatory disorders."

### The British Heart Foundation and Lister Institute for Preventive Medicine-funded study, entitled 'Melanocortin-4-Receptors Reciprocally Regulate Sympathetic and Parasympathetic Preganglionic Neurons' is published in Cell on 31 January 2013.

ELSE PRESS RELEASES FROM THIS DATE:

How cancer cells rewire their metabolism to survive

2013-01-31

LA JOLLA, Calif., January 31, 2013 – Cancer cells need food to survive and grow. They're very good at getting it, too, even when nutrients are scarce. Many scientists have tried killing cancer cells by taking away their favorite food, a sugar called glucose. Unfortunately, this treatment approach not only fails to work, it backfires—glucose-starved tumors actually get more aggressive. In a study published January 31 in the journal Cell, researchers at Sanford-Burnham Medical Research Institute discovered that a protein called PKCζ is responsible for this paradox. The ...

Leading researchers warn of 'brain drain' as scientists struggle to find funding

2013-01-31

Clarksburg, Md. – BrightFocus Foundation, a nonprofit organization that funds research worldwide to save sight and mind, today released the results of a survey of more than 170 leading biomedical scientists that explores the most significant barriers to progress in ending brain and eye diseases. The survey indicates that a lack of dependable funding is threatening to create a deficit of highly skilled scientists at a time when the nation could soon face a health care crisis brought on by devastating disorders like Alzheimer's, macular degeneration, and glaucoma. "Cures ...

A 'neurosteroid' found to prevent brain injury caused by HIV/AIDS

2013-01-31

Bethesda, MD—A team of scientists from Canada, Thailand and Morocco have found that DHEA-S may prevent neurocognitive impairment that affects a significant percentage of AIDS patients. In a report appearing in the February 2013 issue of The FASEB Journal, they describe how a network of steroid molecules found in the brain, termed "neurosteroids," is disrupted during HIV infection leading to brain damage. This suggests that treatment with one of these steroid molecules, called DHEA-S, may offset the disruption caused by the virus to prevent or reduce brain damage. "From ...

Health care providers may be at greater risk of flu exposure

2013-01-31

WINSTON-SALEM, N.C. – Jan. 31, 2013 – Some people with the flu emit more of the air-borne virus than others, suggesting that the current recommendations for infection control among health care providers may not be adequate, according to a new study from researchers at Wake Forest Baptist Medical Center. The study is published in the Jan. 31 online edition of The Journal of Infectious Disease. "Our study provides new evidence that infectiousness may vary between influenza patients and questions the current medical understanding of how influenza spreads," said Werner Bischoff, ...

Gas promises bumper black hole 'weigh-in'

2013-01-31

A new way of measuring the mass of supermassive black holes could revolutionise our understanding of how they form and help to shape galaxies. The technique, developed by a team including Oxford University scientists, can spot the telltale tracer of carbon monoxide within the cloud of gas (mostly hydrogen) circling a supermassive black hole at the centre of a distant galaxy. By detecting the velocity of the spinning gas they are able to 'weigh' (determine the mass) of the black hole. Detailed information on supermassive black holes, thought to be at the heart of most ...

Study finds hormones can change the breast's genetic material

2013-01-31

Melbourne scientists have discovered how female steroid hormones can make dramatic changes to the genetic material in breast cells, changes that could potentially lead to breast cancer. Researchers from the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia, have identified how pregnancy hormones send signals to critical molecules on the DNA to make changes in the epigenome. The epigenome is a series of chemical tags that modify DNA, controlling which genes are switched on and off. Professor Jane Visvader, Dr Bhupinder Pal, Professor Geoff Lindeman ...

Cyclone did not cause 2012 record low for Arctic sea ice

2013-01-31

It came out of Siberia, swirling winds over an area that covered almost the entire Arctic basin in the normally calm late summer. It came to be known as "The Great Arctic Cyclone of August 2012," and for some observers it suggested that the historic sea ice minimum may have been caused by a freak summer storm, rather than warming temperatures. But new results from the University of Washington show that the August cyclone was not responsible for last year's record low for Arctic sea ice. The study was published online this week in Geophysical Research Letters. "The ...

Electronic health records could help identify which patients most need ICU resources

2013-01-31

ANN ARBOR, Mich. — A national shortage of critical care physicians and beds means difficult decisions for healthcare professionals: how to determine which of the sickest patients are most in need of access to the intensive care unit. What if patients' electronic health records could help a physician determine ICU admission by reliably calculating which patient had the highest risk of death? Emerging health technologies – including reliable methods to rate the severity of a patient's condition – may provide powerful tools to efficiently use scarce and costly health resources, ...

International team observe 'hungry twin' stars gobbling their first meals

2013-01-31

AMHERST, Mass. – Just-forming stars, like growing babies, are always hungry and must "feed" on huge amounts of gas and dust from dense envelopes surrounding them at birth. Now a team of astronomers including Robert Gutermuth, a University of Massachusetts Amherst expert in imaging data from the Spitzer Space Telescope, reports observing an unusual "baby" star that periodically emits infrared light bursts, suggesting it may be twins, that is, a binary star. The discovery is reported this month in Nature. The extremely young object, dubbed LRLL 54361, is about 100,000 years ...

Novel materials shake ship scum

2013-01-31

DURHAM, N.C. – Just as horses shake off pesky flies by twitching their skin, ships may soon be able to shed the unwanted accumulation of bacteria and other marine growth with the flick of a switch. Duke University engineers have developed a material that can be applied like paint to the hull of a ship and will literally be able to dislodge bacteria, keeping it from accumulating on the ship's surface. This buildup on ships increases drag and reduces the energy efficiency of the vessel, as well as blocking or clogging undersea sensors. The material works by physically ...

Scientists uncover the first clear evidence of air sacs in the fossilized bones of alvarezsaurian dinosaurs: the "hollow bones" which help modern day birds to fly

Alcohol makes male flies sexy

TB patients globally often incur "catastrophic costs" of up to $11,329 USD, despite many countries offering free treatment, with predominant drivers of cost being hospitalization and loss of income

Scientists identify culprit in obesity-associated high blood pressure

ELSE PRESS RELEASES FROM THIS DATE:

LAST 30 PRESS RELEASES: