Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

HSPH researchers discover natural inflammation-fighting mechanism in body-fat cells

05.06.2008
Protective mechanism fails when obesity sets in

Scientists have discovered a previously unknown molecular signaling pathway in body fat cells that normally acts to suppress harmful inflammation. Cellular stress caused by obesity, however, can override this protective function and convert the pathway into a trigger of chronic inflammation that raises the risk of insulin resistance, diabetes, and other metabolic disorders.

Reporting in the journal Cell Metabolism, researchers from the Harvard School of Public Health (HSPH) said they have shown for the first time that fat-storing cells, or adipocytes, contain a protective anti-inflammatory immune mechanism that prevents the cells from over-reacting to inflammation-causing stimuli, such as fatty acids in the diet.

This signaling pathway serves as a natural counterbalance to a parallel signaling chain that promotes inflammation and can lead to insulin resistance -- a prelude to diabetes -- and other ailments such as heart disease, said the authors. Chih-Hao Lee, Assistant Professor of Genetics and Complex Diseases at HSPH, was the senior author. Kihwa Kang, Research Fellow in the HSPH Department of Genetics and Complex Diseases, was first author.

In lean people, the dueling pathways maintain a healthy balance -- but only up to a point. "Overt obesity eventually overwhelms the protective effect of this pathway and flips it into the pro-inflammatory pathway," said Lee.

The scientists also identified the molecular switch that determines which pathway is activated under different conditions. It may be possible, they suggest, to develop drugs that would boost the protective side of the two-pronged mechanism to more strongly suppress inflammation and reduce the risk of insulin resistance, diabetes, or other ailments.

In identifying the compensatory pathway and molecular switch, the scientists have added a new element to the growing understanding of how obesity exerts its unhealthful effects through signals generated by adipocytes.

Previous research, including important discoveries by Gökhan Hotamisligil, chair of the HSPH Department of Genetics and Complex Diseases, has shown that as they become enlarged with fat, adipocytes produce pro-inflammatory stimuli, such as free fatty acids. These stimuli induce the activation of immune cells residing within fat tissues, called M1 macrophages, which in turn release pro-inflammatory cytokines, such as TNFalpha, that cause fat tissue dysfunction and insulin resistance. Cytokines are messenger chemicals that enable communication between immune cells but could also be produced by fat cells.

Another type of macrophage, known as M2, has the opposite effect, quelling the inflammatory response to free fatty acids. The process that induces M2 macrophages is known as "alternative activation." Until now, the mechanisms controlling M2 macrophage activation within fat tissues had been unclear, as was whether adipocytes themselves controlled this process. The results reported in Lee's paper, said Hotamisligil (who was not involved in the research), indicate that "the adipocytes actually force macrophages to go one way or the other."

What activates the M2 pathway within fat tissues, Lee and his colleagues discovered, is the fat cells' production of the kind of cytokines that activate M2 macrophages. These so-called "Th2" cytokines include IL 13 and IL4. (M1 macrophages are activated by a different set of cytokines.)

The researchers found that the key to the Th2 activation switch is a molecule known as PPAR-d within macrophages. PPAR-d is a "nuclear receptor" that receives the Th2 cytokine signals and turns on a cascade of genes and proteins that results in M2 macrophage activation.

Experiments showed that mice in which the PPAR-D function was knocked out could not switch on the M2 macrophage pathway. When fed a high-fat diet, those mice became obese and developed insulin resistance, confirming the key role of PPAR-d as a switch governing the two pathways.

To their surprise, Lee and his coworkers found that the same switching mechanism is present in hepatocytes, or liver cells, and macrophages in the liver, where they control metabolism of fats. Mice lacking PPAR-d developed the condition known as "fatty liver," which also occurs in humans who have metabolic disruption.

Given the enormous problem of obesity and diabetes in the United States and elsewhere, Lee is hopeful that drugs targeting PPAR-d may be useful in treating insulin resistance and diabetes. And now that the same mechanism has been identified in liver cells, the same strategy might lead to novel therapies for fatty liver. Finally, the link between obesity, inflammation and atherosclerosis suggests that PPAR-d-targeted drugs could have potential in preventing heart disease as well.

Christina Roache | EurekAlert!
Further information:
http://www.hsph.harvard.edu

Further reports about: Cells Cytokine Diabetes HDL-cholesterol HSPH Insulin PPAR-d adipocytes inflammation liver macrophage obesity protective

More articles from Life Sciences:

nachricht Closing the carbon loop
08.12.2016 | University of Pittsburgh

nachricht Newly discovered bacteria-binding protein in the intestine
08.12.2016 | University of Gothenburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Closing the carbon loop

08.12.2016 | Life Sciences

Applicability of dynamic facilitation theory to binary hard disk systems

08.12.2016 | Physics and Astronomy

Scientists track chemical and structural evolution of catalytic nanoparticles in 3-D

08.12.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>