Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene mutation causes lethally low-fat diet

05.04.2006
We are all familiar with the dangers of too much fat in our diet--increased risk of diabetes, heart disease, and obesity are just a few of the most severe consequences.

But some rare metabolic diseases, such as hypolipidemia and Tangier disease, seem to work in reverse--they severely limit the amount of fat and cholesterol that makes it into the bloodstream. Researchers from the Carnegie Institution and the University of Pennsylvania have found a specific gene that could be responsible for such conditions; when the gene is disrupted, so is the ability to absorb lipids (fatty substances that include cholesterol) through the intestine.


Zebrafish larvae with a lethal mutation affecting fat metabolism (ffr) look the same as normal larvaes (wt) under normal magnification (left). However, when the embryos ingest lipid molecules labeled with...

In their latest research, published in the April 4 issue of the journal Cell Metabolism, Steve Farber of Carnegie’s Department of Embryology and Michael Pack, of the University of Pennsylvania School of Medicine describe their efforts to locate a gene called fat free within the genome of the zebrafish. These fish have become popular research organisms because their embryos are transparent, allowing studies that are not possible with traditional model organisms, such as mice and rats. Farber and Pack found that, despite the distant evolutionary relation between humans and zebrafish, the fat free gene in zebrafish is quite similar to a pair of human genes.

The researchers also explore the physical effects of a specific mutation of the gene, seeking to explain why larval fish with the mutation exhibit an impaired ability to absorb cholesterol. These fish die when they are about a one-and-a-half weeks old because of this defect, even though they look normal and swallow properly.

"There is a lot we still don’t know about how animals absorb, transport, and otherwise manage lipids," Farber said. "The fact that just one gene can have such a huge effect is encouraging, because it might reveal a means for treatment of human disease."

The scientists began by looking for structural defects in the mutants’ digestive organs. Their livers have abnormalities in the cells and ducts that produce bile--a salty, somewhat soapy fluid that helps lipid digestion. Certain pancreatic cells are also flawed, interfering with the production of digestive enzymes necessary for the breakdown of complex lipid molecules.

More importantly, the mutants also have defects in the cells that line the intestine, where fat and cholesterol absorption takes place. Normally, globules of lipid pass into these cells in small sacs called vesicles. These vesicles connect with the Golgi apparatus, a labyrinth of membranes filled with enzymes that modify the fats, and then new vesicles transport the fats out of the cell and into the bloodstream. The researchers found that this process is disrupted in the fat free mutants, preventing fats from reaching the bloodstream, and thereby depriving the animal of needed lipids.

Farber and Pack used a strategy called positional cloning both to locate fat free in the zebrafish genome and to determine its sequence. They found that the gene shares 75 percent of its sequence with a human gene called ANG2 (Another New Gene 2), which up to this time has had no known function. It also shares parts of its sequence with a gene called COG8, which is known to affect the Golgi apparatus. They also found that a change in only one base--one "letter" in the DNA code--results in the lethal mutation in zebrafish.

"This gene is absolutely necessary for cholesterol absorption--without it, the animals die," Farber said. This is encouraging for Pack, a physician-scientist in Penn’s Department of Medicine, "If we can understand this process in zebrafish, perhaps we can take what we learn and apply it to similar genes in humans, which could in turn lead to treatment for lipid metabolism disorders."

Dr. Steven Farber | EurekAlert!
Further information:
http://www.ciwemb.edu
http://www.carnegieinstitution.org/

More articles from Life Sciences:

nachricht Closing in on advanced prostate cancer
13.12.2017 | Institute for Research in Biomedicine (IRB Barcelona)

nachricht Visualizing single molecules in whole cells with a new spin
13.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

A whole-body approach to understanding chemosensory cells

13.12.2017 | Health and Medicine

Water without windows: Capturing water vapor inside an electron microscope

13.12.2017 | Physics and Astronomy

Cellular Self-Digestion Process Triggers Autoimmune Disease

13.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>