Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Why do fat cells get fat? New suspect ID'd

26.06.2012
Surprising finding about WNT signaling points to Sfrp5 as a potential target for anti-obesity drugs

As the world fights obesity at the human level, scientists at the University of Michigan and their colleagues have made a surprising finding at the microscopic level that could help fuel that fight.

Their work helps explain why fat-storing cells get fatter, and burn fat slower, as obesity sets in. If their findings from mice can be shown to apply to humans, they may provide a new target for obesity-fighting drugs.

By studying the tiny signals that fat-storing cells send to one another, the team has shown a crucial and previously unknown role for a molecule called Sfrp5.

The results, which appear online today and will be in the July issue of the Journal of Clinical Investigation, surprised them.

In a series of experiments, the team showed that Sfrp5 influences a signaling pathway known as WNT to stimulate fat cells – called adipocytes – to grow larger and to suppress the rate at which fat is burned in the mitochondria inside them.

By stopping cells from making Sfrp5, they were able to make mice that didn't get as fat as quickly because their adipocytes didn't grow large – even when the mice were fed a high-fat diet. They even showed the impact when transplanting fat from Sfrp5—deficient mice into other mice.

The research was performed with National Institutes of Health funding in the U-M Medical School laboratory of Ormond MacDougald, Ph.D., the Faulkner Professor in the Department of Molecular & Integrative Physiology, a professor of internal medicine and a member of U-M's Brehm Center for Diabetes Research.

Working with postdoctoral fellow and first author Hiroyuki Mori, Ph.D., and colleagues, MacDougald says the team built on its previous findings about the importance of WNT signaling in fat cell development.

"WNT signaling plays a crucial role in regulating, and inhibiting, white fat cell growth and the recruitment of new cells to store fat," he explains. "But it appears that in obesity, Sfrp5 can interfere with that signaling, and may create a feedback loop that keeps stimulating production of more of itself."

He notes that the new results contradict previous work published by another group, which found essentially the opposite role for Sfrp5. A commentary accompanying the new U-M paper, by scientists from Denmark, notes the strong evidence behind the new findings and emphasizes the importance of further research on the topic.

MacDougald and his team zeroed in on Sfrp5 after years of studying WNT signaling between adipocytes. They and other teams had already seen that the amounts of Sfrp5 produced within fat tissue were higher in obese animals.

They were able to breed mice that could not make the molecule, and expected to see that these mice resisted obesity because they couldn't convert more cells into adipocytes to store excess fat from their high-fat diet.

But instead, they found that the mice without Sfrp5 did have just as many fat cells as other mice -- but that these cells didn't accumulate fat and grow bigger. As a result, the mice didn't get fat, no matter how rich their diet.

Looking more closely at Sfrp5-deficient mice, they saw a surge of activity in expression of genes related to mitochondria – the furnaces inside cells that burn fat or other fuel to power cell activity. It was as if the furnaces had been stoked when Sfrp5 wasn't present, so fat could be burned at a higher rate than normal.

"From our results, we believe that Sfrp5 is an important moderator of mitochondrial activity, the first time this has been seen for the WNT signaling pathway in adipocytes," says Mori. "This underscores the complexity of WNT signaling."

In essence, MacDougald says, Sfrp5 poses as a decoy receptor for WNT signals to bind to, keeping them from binding to the receptors on the cell surface that they otherwise would bind to. With WNT signaling reduced, cells store fat and grow larger, and don't burn it as quickly. Then, the cells produce even more Sfrp5, creating the feedback loop that perpetuates the tendency for adipocytes to accumulate lipid.

While pharmaceutical companies are already looking at WNT signaling as a possible target for drugs related to bone formation, the new findings suggest that perhaps the same signaling pathway could be a target for anti-obesity drugs.

But, MacDougald cautions, the findings need to be explored further in both mice and humans. With the obesity epidemic putting hundreds of millions of people at risk of all types of diseases, that research has a special urgency behind it.

In addition to MacDougald and Mori, the research team included Tyler C. Prestwich, who received a Ph.D. from U-M's Cell and Molecular Biology program and is a co-first author, Michael A. Reid, former U-M postdoctoral fellow and Proteostasis Therapeutics employee Kenneth Longo, former postdoctoral fellow Isabelle Gerin, current fellow William Cawthorn, Vedrana S. Susulic, Venkatesh Krishnan, and Andy Greenfield.

The work was supported by grants DK51563 and DK62876 from the NIH's National Institute for Diabetes and Digestive and Kidney Diseases, and by Mori's mentor-based postdoctoral fellowship from the American Diabetes Association. The team used two core research facilities at the U-M Medical School: the Animal Phenotyping Core of the Nutrition Obesity Research Center, supported by NIH grant DK089503, and the Morphology Core of the Michigan Diabetes Research and Training Center, supported by NIH grant P60DK020572.

Reference: Journal of Clinical Investigation http://www.jci.org Vol. 122 No. 7, July 2012, Online ahead of print - doi:10.1172/JCI63604

Kara Gavin | EurekAlert!
Further information:
http://www.umich.edu

More articles from Life Sciences:

nachricht Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

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 “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>