Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Johns Hopkins scientists exploit novel route to reverse enlarged hearts in obese mice

07.03.2006


Nerve growth factor makes end run around leptin, a brain hormone linked to appetite regulation



Working on genetically engineered obese mice with seriously thickened hearts, a condition call cardiac hypertrophy, scientists at Johns Hopkins have used a nerve protection and growth factor on the heart to mimic the activity of the brain hormone leptin, dramatically reducing the size of the heart muscle.

Leptin is a protein hormone made by fat cells that signals the brain to stop eating. Alterations in the leptin-making gene may create leptin deficiency linked to obesity and other defects in weight regulation.


By injecting so-called ciliary neurotrophic factor (CNTF) into mice that were either deficient in or resistant to leptin, the researchers reduced the animals’ diseased and thickened heart muscle walls by as much as a third and the overall size of the left ventricle, the main pumping chamber, up to 41 percent, restoring the heart’s architecture toward normal.

Enlarged hearts lead to heart failure and death. Results of the study, supported in part by the National Institutes of Health, are to be published in the March 6 issue of the Proceedings of the National Academy of Sciences.

"These findings suggest there’s a novel brain-signaling pathway in obesity-related heart failure and have therapeutic implications for patients with some forms of obesity-related cardiovascular disease," says study senior author Joshua M. Hare, M.D., a professor and medical director of the heart failure and cardiac transplantation programs at The Johns Hopkins University School of Medicine and its Heart Institute.

Most obesity in people is associated with an inability to use leptin made naturally in the body, says Hare, who also is director of the cardiovascular section of Hopkins’ Institute for Cellular Engineering.

"We knew that leptin supplements wouldn’t address obesity-linked heart disease, but reasoned that CNTF might be a way to get around leptin resistance by activating a related signaling pathway with similar effects on body weight and metabolism," he says.

Hare and his colleagues tested the idea on mice with left ventricular hypertrophy (LVH), a condition in which the left ventricle expands and stiffens, preventing proper blood flow to the body. In humans, obesity is a major risk factor for LVH, which results from stress on the heart. As the heart muscle is worked harder, it bulks up.

"Our finding that CNTF causes LVH to regress not only in leptin-deficient animals but also in those lacking a functional leptin receptor establishes the existence of a new pathway to help regulate LVH," Hare says.

For the study, Hare and colleagues first examined whether CNTF receptors were present and functional in the heart muscles by staining heart muscle cells with a chemical that would highlight the receptors when viewed under a high-powered microscope. These tests showed that CNTF receptors were located on the cells’ surfaces.

Next, they randomly assigned a set of leptin-deficient mice into three groups: a third received daily abdominal injections of CNTF, a third were fed a calorie-restricted diet, and a third ate as much as they wanted. The researchers used the same three approaches plus leptin supplements on another group of leptin-resistant mice.

Ultrasound exams of the hearts after four weeks showed that CNTF decreased the thickness of the wall dividing the heart chambers by as much as 27 percent, decreased the thickness of the wall at the back of the heart by as much as 29 percent and overall volume of the left ventricle by as much as 41 percent. As expected, leptin supplements did not change left ventricular wall thickness.

CNTF-treated mice also showed reduced heart-cell width, a direct measure of the amount of hypertrophy.

More research is to be done before CNTF can be used to treat patients, Hare says, as people can develop antibodies to CNTF. The scientists next plan to test CNTF in other animal models of hypertrophy not related to obesity.

David March | EurekAlert!
Further information:
http://www.jhmi.edu

More articles from Life Sciences:

nachricht How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>