Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Disabling enzyme allows mice to gorge without becoming obese

13.01.2009
Researchers at the University of California, Berkeley, have identified a new enzyme that plays a far more important role than expected in controlling the breakdown of fat. In a new study to be published Jan. 11 in the journal Nature Medicine, researchers report that mice that have had this enzyme disabled remained lean despite eating a high-fat diet and losing a hormone that suppresses appetite.

"We have discovered a new enzyme within fat cells that is a key regulator of fat metabolism and body weight, making it a promising target in the search for a treatment for human obesity," said Hei Sook Sul, UC Berkeley professor of nutritional sciences and toxicology and principal investigator of the research.

Sul's research team includes the three co-lead authors of the paper, all from UC Berkeley's Department of Nutritional Sciences and Toxicology: Kathy Jaworski, former post-doctoral researcher; Maryam Ahmadian, graduate student; and Robin Duncan, post-doctoral fellow.

The enzyme in the spotlight, adipose-specific phospholipase A2 (AdPLA), is found in abundance only in fat tissue. AdPLA sets off a chain of events that increases levels of a signaling molecule called prostaglandin E2 (PGE2), which suppresses the breakdown of fat. Mice that have no AdPLA have lower PGE2 levels and a higher rate of fat metabolism.

"When levels of PGE2 are decreased because of the lack of AdPLA, fat breakdown proceeds unchecked, resulting in leanness even in animals that eat all day long," said co-lead author Duncan.

In the study, mice that had the gene for AdPLA expression knocked out were compared with a control group of normal mice. As soon as the mice were weaned at about 3 weeks of age, researchers began offering the two groups of mice an all-you-can-eat buffet of tasty, high-fat foods.

Notably, the enzyme did not appear to affect appetite since the two groups ate equivalent amounts. However, as the mice aged, the disparity in weight gain became clear. By 64 weeks of age - considered the twilight years in a lab mouse's lifespan - the mice that lacked the AdPLA enzyme averaged only 39.1 grams, a weight more typical of a low-fat diet, while the control mice weighed in at a hefty 73.7 grams.

The researchers noted that the missing AdPLA did not change the number of fat cells, but simply kept the cells from accumulating excess fat.

The researchers also studied whether loss of AdPLA could prevent genetic obesity in mice. They compared mice that lacked leptin, the hormone that signals when the body is full, with mice that lacked both AdPLA and leptin. Leptin-deficient mice are voracious eaters, typically consuming two to three times more food per day than normal mice, and they rapidly develop obesity.

In this study, leptin-deficient mice ate an average of 5 grams of food per day, while mice that lacked both AdPLA and leptin ate 7.5 grams. Typically, normal mice will eat only 2-3 grams per day. By 17 weeks of age, the leptin-deficient mice were already hitting the scales at 75 grams. In comparison, mice that lacked both AdPLA and leptin weighed just under 35 grams.

The researchers found that levels of AdPLA increase after eating to block fat breakdown, and decrease with fasting to allow fat breakdown to proceed efficiently. They also found that levels of AdPLA are higher in obese mice.

"This means that local signals in fat tissue allow fat cells to directly regulate fuel provision for the body, which changes our fundamental understanding of how the body regulates fat breakdown," said Ahmadian, another study co-lead author. "We found that mice deficient in AdPLA expend more energy than normal mice, and they also burn more fat directly within fat cells."

Before this paper, the assumption had been that the major players in controlling fat metabolism and body weight were endocrine factors, primarily hormones that are secreted by different organs and glands and travel through the bloodstream to fat tissue, the authors said.

The new findings show that a large portion of the action is occurring within the actual fat tissue, mainly through the autocrine and paracrine action of PGE2 that acts locally within a cell or small group of cells.

The researchers caution that previous discoveries in fat metabolism and appetite regulation have not always translated well from mice to humans. Although some people have mutations in the gene that codes for AdPLA, it remains to be seen what effect these mutations have in humans, they said.

They also noted that inhibiting the expression of AdPLA in mice led to greater insulin resistance and a four-fold increase in fat content in the liver. However, tests of liver function were largely normal.

Nevertheless, AdPLA may become an attractive target in developing a treatment to combat obesity, the researchers said. If excess fat can be burned before it escapes the fat cell, it can never get into the bloodstream to negatively affect other organs, such as the heart.

"We believe that the effects in the liver are due to the extremely high rate of fat breakdown and drastic leanness in these mice, so we are looking to see if reducing rather than completely eliminating AdPLA can provide effective protection against obesity without secondary effects," said Duncan.

Sarah Yang | EurekAlert!
Further information:
http://www.berkeley.edu

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

DGIST develops 20 times faster biosensor

24.04.2017 | Physics and Astronomy

Nanoimprinted hyperlens array: Paving the way for practical super-resolution imaging

24.04.2017 | Materials Sciences

Atomic-level motion may drive bacteria's ability to evade immune system defenses

24.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>