Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Hyperactive Mice Eat All They Want, but Have Low Body Fat

29.06.2004


Genetically engineered mice, created at the University of Michigan Medical School, are living every dieter’s dream. They eat unlimited amounts of high-fat mouse chow, but have about 50 percent less body fat than normal mice on a low-fat diet. And they show no signs of diabetes or other metabolic disorders, which are common in animals with too little fat.

But don’t stock up on potato chips and ice cream just yet. The genetically altered mice are leaner than normal mice, but they also have some less-than-desirable characteristics – such as underdeveloped mammary glands, an inability to generate body heat and skin that’s twice as thick as normal.

All these changes appear to be caused by a protein called Wnt10b, which is present in artificially high amounts in fat tissue from the experimental mice. Wnt10b is one of a family of 19 related proteins. Wnts (pronounced “wints”) regulate the complex changes that take place as an embryo grows. Part of this process is the development of fatty adipose tissue, which contains fat cells called adipocytes.



Ormond A. MacDougald, Ph.D., an associate professor of molecular and integrative physiology in the U-M Medical School, has spent years studying the effects of Wnt10b on the development of adipocytes. In August 2000, MacDougald and his colleagues published a paper in Science, showing that Wnt10b gene activity repressed fat cell development in tissue cultures.

Now, in the first study in living animals, MacDougald and Kenneth A. Longo, Ph.D, a U-M research fellow in physiology, have demonstrated that Wnt10b has the same effect on fatty tissue in mice.

“High levels of Wnt10b expression produced animals with 50 percent less body fat and fewer fat cells, regardless of whether the mice ate a high-fat or low-fat diet,” MacDougald says.

Results of the U-M experiments were posted this month on the Journal of Biological Chemistry’s “JBC Online” Web site (see URL at the end of this press release).

“To determine the effect of the gene on adipose tissue development, we created an artificial sequence of DNA called a transgene linking Wnt10b to another gene called the FABP4 promoter, which is expressed only in adipose tissue,” Longo says. “We injected the transgene DNA into fertilized mouse eggs and bred mice that inherited the new gene to create the animals used in our study. Under the control of the FABP4 promoter, fatty tissue in the transgenic mice contained 50 times the amount of Wnt10b found in adipose tissue from normal mice.”

Longo and MacDougald discovered that Wnt10b had a different effect on the two types of fat found in normal mice. White fat is a storage reservoir for excess energy. Brown fat is a specialized form of adipose tissue, found in small mammals and human newborns, which generates heat to keep the animal warm. While the transgenic mice in the U-M study had half as much white fat as normal mice, they had virtually no brown fat at all. This made it impossible for them to maintain their core body temperature, leaving them very vulnerable to cold.

For reasons U-M scientists don’t understand, the transgenic mice had skin that was twice as thick and much heavier than normal mice. Another puzzling and unexpected finding from the study was that the transgenic mice consumed slightly less oxygen.

But perhaps the most surprising thing about the U-M’s transgenic mice was their general state of robust good health.

“When we started making these animals, we thought they would have reduced amounts of fat, and thus suffer from metabolic complications, including diabetes,” Longo says. “Adipose tissue produces proteins, such as leptin and adiponectin, which affect the body’s ability to respond to insulin. Reduced insulin sensitivity is one of the first symptoms of diabetes. So having little or no white fat is just as devastating to your health as having too much fat.”

“Even though the Wnt10b transgenic mice had half as much adipose tissue and produced half the normal amount of leptin, they had none of the metabolic consequences we expected,” MacDougald says. “In fact, the insulin sensitivity and glucose tolerance of transgenic mice on a high-fat diet was better than that of normal mice on a low-fat diet. We don’t know why, but additional research should provide some answers.”

Currently, researchers in MacDougald’s lab are studying the effect of Wnt proteins on mice with genetically induced obesity. They also plan to explore the effect of Wnt signaling on the development of osteoblasts, the bone-forming cells in marrow.

But don’t look for Wnt10b diet pills to be on the market any time soon, cautions Longo and MacDougald.

“Pharmaceutical companies are interested in the potential therapeutic role of Wnt genes in decreasing fatty tissue, but finding the right drug to selectively target this pathway without complications will be a considerable challenge,” MacDougald says. “The goal of our research is to learn how fat cell development is regulated, but this work may also improve our understanding of obesity and its complications.”

“We’ve seen the potent effect of Wnt10b on fat in mice, but we don’t know if it would work the same way in humans,” Longo adds. “And, if the results we see in the skin of the transgenic mice are any indication, I’d say we have to tread carefully. I think we’d all like to be thicker-skinned, but only in the figurative sense.”

The research was funded by the National Institutes of Health, the U-M Center for Integrative Genomics, the U-M Center for Organogenesis, the U-M Diabetes Research and Training Center and the American Diabetes Association.

The experimental mice used in the study were produced in the U-M’s Transgenic Animal Model Core facility. The University has filed for patent protection on the Wnt10b transgenic mouse.

U-M study collaborators included Wendy S. Wright, research associate; Sona Kang, graduate student; Isabelle Gerin, Ph.D., and Shian-Huey Chiang, Ph.D., post-doctoral fellows; Peter C. Lucas, M.D., Ph.D., lecturer in pathology; and Mark R. Opp, Ph.D., associate professor of anesthesiology and of molecular and integrative physiology.

| newswise
Further information:
http://www.med.umich.edu

More articles from Health and Medicine:

nachricht Why might reading make myopic?
18.07.2018 | Universitätsklinikum Tübingen

nachricht Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University

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: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Global study of world's beaches shows threat to protected areas

19.07.2018 | Earth Sciences

New creepy, crawly search and rescue robot developed at Ben-Gurion U

19.07.2018 | Power and Electrical Engineering

Metal too 'gummy' to cut? Draw on it with a Sharpie or glue stick, science says

19.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>