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 When wheels and heads are spinning - DFG research project on motion sickness in automated driving
22.05.2019 | Technische Universität Berlin

nachricht A new approach to targeting cancer cells
20.05.2019 | University of California - Riverside

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: Self-repairing batteries

UTokyo engineers develop a way to create high-capacity long-life batteries

Engineers at the University of Tokyo continually pioneer new ways to improve battery technology. Professor Atsuo Yamada and his team recently developed a...

Im Focus: Quantum Cloud Computing with Self-Check

With a quantum coprocessor in the cloud, physicists from Innsbruck, Austria, open the door to the simulation of previously unsolvable problems in chemistry, materials research or high-energy physics. The research groups led by Rainer Blatt and Peter Zoller report in the journal Nature how they simulated particle physics phenomena on 20 quantum bits and how the quantum simulator self-verified the result for the first time.

Many scientists are currently working on investigating how quantum advantage can be exploited on hardware already available today. Three years ago, physicists...

Im Focus: Accelerating quantum technologies with materials processing at the atomic scale

'Quantum technologies' utilise the unique phenomena of quantum superposition and entanglement to encode and process information, with potentially profound benefits to a wide range of information technologies from communications to sensing and computing.

However a major challenge in developing these technologies is that the quantum phenomena are very fragile, and only a handful of physical systems have been...

Im Focus: A step towards probabilistic computing

Working group led by physicist Professor Ulrich Nowak at the University of Konstanz, in collaboration with a team of physicists from Johannes Gutenberg University Mainz, demonstrates how skyrmions can be used for the computer concepts of the future

When it comes to performing a calculation destined to arrive at an exact result, humans are hopelessly inferior to the computer. In other areas, humans are...

Im Focus: Recording embryonic development

Scientists develop a molecular recording tool that enables in vivo lineage tracing of embryonic cells

The beginning of new life starts with a fascinating process: A single cell gives rise to progenitor cells that eventually differentiate into the three germ...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

First dust conference in the Central Asian part of the earth’s dust belt

15.04.2019 | Event News

 
Latest News

Summit charts a course to uncover the origins of genetic diseases

22.05.2019 | Life Sciences

New study finds distinct microbes living next to corals

22.05.2019 | Life Sciences

Stellar waltz with dramatic ending

22.05.2019 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>