Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

White blood cell enzyme contributes to inflammation and obesity

03.04.2013
An imbalance between an enzyme called neutrophil elastase and its inhibitor causes inflammation, obesity, insulin resistance, and fatty liver in mice and humans -- providing a new therapeutic target for these health conditions

Many recent studies have suggested that obesity is associated with chronic inflammation in fat tissues. Researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) have discovered that an imbalance between an enzyme called neutrophil elastase and its inhibitor causes inflammation, obesity, insulin resistance, and fatty liver disease.

This enzyme is produced by white blood cells called neutrophils, which play an important role in the body's immune defense against bacteria. The researchers found that obese humans and mice have increased neutrophil elastase activity and decreased levels of á1-antitrypsin, a protein that inhibits the elastase. When the team reversed this imbalance in a mouse model and fed them a high-fat diet, the mice were resistant to body weight gain, insulin resistance (a precursor to type 2 diabetes), and fatty liver disease. Their study appears April 2 in Cell Metabolism.

"The imbalance between neutrophil elastase and its inhibitor, á1-antitrypsin, is likely an important contributing factor in the development of obesity, inflammation, and other health problems. Shifting this balance—by either reducing one or increasing the other—could provide a new therapeutic approach to preventing and treating obesity and several obesity-related conditions," said Zhen Jiang, Ph.D., assistant professor in Sanford-Burnham's Diabetes and Obesity Research Center at Lake Nona, Orlando and senior author of the study.

What happens when you reduce neutrophil elastase levels

This study began when Jiang and his team noticed that neutrophil elastase levels are particularly high and á1-antitrypsin levels are low in a mouse model of obesity. Then they saw the same thing in blood samples from human male volunteers.

To further probe this curious neutrophil elastase-obesity relationship, the researcher turned once again to mouse models. They found that mice completely lacking the neutrophil elastase enzyme don't get as fat as normal mice, even when fed a high-fat diet. Those mice were also protected against inflammation, insulin resistance, and fatty liver. The same was true in a mouse model genetically modified to produce human á1-antitrypsin, which inhibits neutrophil elastase.

Normal mice on a high-fat diet were also protected against inflammation, insulin resistance, and fatty liver when they were given a chemical compound that inhibits neutrophil elastase. This finding helps validate the team's conclusions about neutrophil elastase's role in inflammation and metabolism and also suggests that a medicinal drug could someday be developed to target this enzyme.

Mechanism: how neutrophil elastase influences inflammation and metabolism

How do high neutrophil elastase levels increase inflammation and cause weight gain and other metabolic problems?

Jiang and his team began connecting the mechanistic dots. They discovered that neutrophil elastase-deficient mice have increased levels of several factors, including adiponectin, AMPK, and fatty acid oxidation. These are known for their roles in increasing energy expenditure, thus helping the body burn excess fat.

This research was funded by a Sanford-Burnham start-up fund, the American Diabetes Association (grant 7-11-BS-72), U.S. National Institutes of Health (National Institute of Diabetes and Digestive and Kidney Diseases grant R01DK094025), and U.K. Medical Research Council (grant U117512772).

The study was co-authored by Virginie Mansuy-Aubert, Sanford-Burnham; Qiong L. Zhou, Sanford-Burnham; Xiangyang Xie, Sanford-Burnham; Zhenwei Gong, Sanford-Burnham; Jun-Yuan Huang, Sanford-Burnham; Abdul R. Khan, Sanford-Burnham, National Institute for Biotechnology and Genetic Engineering, Pakistan; Gregory Aubert, Sanford-Burnham; Karla Candelaria, Sanford-Burnham; Shantele Thomas, Sanford-Burnham; Dong-Ju Shin, Sanford-Burnham; Sarah Booth, U.K. National Institute of Medical Research; Shahid M. Baig, National Institute for Biotechnology and Genetic Engineering, Pakistan; Ahmed Bilal, Allied Hospital, Punjab Medical College; Daehee Hwang, Institute for Systems Biology; Hui Zhang, Institute for Systems Biology, Johns Hopkins University; Robin Lovell-Badge, U.K. National Institute of Medical Research; Steven R. Smith, Sanford-Burnham, Translational Research Institute, Florida Hospital; Fazli R. Awan, National Institute for Biotechnology and Genetic Engineering, Pakistan; Zhen Y. Jiang, Sanford-Burnham

About Sanford-Burnham Medical Research Institute

Sanford-Burnham Medical Research Institute is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. Sanford-Burnham takes a collaborative approach to medical research with major programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is recognized for its National Cancer Institute-designated Cancer Center and expertise in drug discovery technologies. Sanford-Burnham is a nonprofit, independent institute that employs 1,200 scientists and staff in San Diego (La Jolla), California and Orlando (Lake Nona), Florida. For more information, visit us at sanfordburnham.org.

Heather Buschman | EurekAlert!
Further information:
http://www.sanfordburnham.org

More articles from Life Sciences:

nachricht Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside

nachricht Chlamydia: How bacteria take over control
28.03.2017 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Researchers create artificial materials atom-by-atom

28.03.2017 | Physics and Astronomy

Researchers show p300 protein may suppress leukemia in MDS patients

28.03.2017 | Health and Medicine

Asian dust providing key nutrients for California's giant sequoias

28.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>