Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gladstone scientists identify target that may reduce complications of obesity

04.02.2010
Although obesity is a risk factor for diabetes and coronary heart disease worldwide, only some obese individuals go on to develop these metabolic complications, while others are relatively protected. Defining these protective factors could help scientists prevent disease in the wider population.

To this end, a research team at the Gladstone Institute of Cardiovascular Disease, led by Suneil Koliwad, MD, PhD, recently added new details that link obesity to diabetes and heart disease.

When individuals become obese from overeating, cells called adipocytes located in the fat tissue fill up with dietary fats and begin to die. Immune cells called macrophages move out of the blood stream and into this tissue, where they accumulate around dying adipocytes. As the macrophages work to clear away the dead cells, they are exposed to large amounts of dietary fat that can result in unwanted consequences. Exposure to saturated fats, in particular, causes the macrophages to enter an inflammatory state. In this state, the macrophages secrete cytokines, such as tumor necrosis factor (TNF) alpha, that encourage the development of insulin resistance, diabetes, and heart disease.

The Gladstone team hypothesized that enhancing the capacity of macrophages to store dietary fats might alter this process. To do this, they focused on an enzyme called DGAT1, which makes triglycerides from dietary fats for storage as cellular energy reserves.

They examined a transgenic strain of mice (aP2-Dgat1) that make large amounts of DGAT1 in both adipocytes and macrophages. On a high-fat diet, these mice became obese, but the macrophages in their fat tissue did not undergo inflammatory activation, and the mice were protected from developing systemic inflammation, insulin resistance, and fatty livers, all problems that were profound in the control mice.

Even more interesting was the team's finding that the protection against diet-induced inflammation and insulin resistance could be conferred on normal mice simply by replacing their macrophages with those from aP2-Dgat1 mice by bone marrow transplantation.

"We found in experimental mice that a single enzyme, DGAT1, in macrophages is involved in many of the problems associated with obesity," said Dr. Koliwad. "This is exciting because humans have this enzyme as well, providing the potential for a therapeutic target to examine."

Using cultured cells, the team also showed that increasing the amount of DGAT1 expressed by macrophages increased their capacity to store triglycerides and protected them against inflammatory activation by saturated fats. Moreover, DGAT1 expression was increased by treatment of macrophages with PPARgamma agonists, which are widely used agents to treat diabetes, and DGAT1 was required for these agents to protect macrophages against inflammatory activation induced by saturated fats.

"Our results are very exciting," said Dr. Robert Farese, senior author on the study. "We have used DGAT1 as a tool to uncover a mechanism by which macrophages might protect individuals from developing serious consequences of obesity."

Koliwad SK, Streeper RS, Monetti M, Cornelissen I, Chan L, Terayama K, Naylot S, Rao M, Hubbard B, Farese RV, Jr. Increased capacity for triacylglycerol synthesis in macrophages protects mice from deleterious consequences of diet-induced obesity. J. Clin. Invest., In press.

Robert V. Farese's primary affiliation is with the Gladstone Institute of Cardiovascular Disease, where he is senior investigator and where his laboratory is located and his research is conducted. He is also a professor of medicine, biochemistry and biophysics at the University of California, San Francisco.

About the Gladstone Institutes. The Gladstone Institutes is a nonprofit, independent research and educational institution, consisting of the Gladstone Institute of Cardiovascular Disease, the Gladstone Institute of Virology and Immunology and the Gladstone Institute of Neurological Disease. Independent in its governance, finances and research programs, Gladstone shares a close affiliation with UCSF through its faculty, who hold joint UCSF appointments.

Valerie Tucker | EurekAlert!
Further information:
http://www.ucsf.edu

More articles from Health and Medicine:

nachricht Improving memory with magnets
28.03.2017 | McGill University

nachricht Graphene-based neural probes probe brain activity in high resolution
28.03.2017 | Graphene Flagship

All articles from Health and Medicine >>>

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

Transport of molecular motors into cilia

28.03.2017 | Life Sciences

A novel hybrid UAV that may change the way people operate drones

28.03.2017 | Information Technology

NASA spacecraft investigate clues in radiation belts

28.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>