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."
Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg
Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
23.02.2018 | Physics and Astronomy
23.02.2018 | Health and Medicine
23.02.2018 | Physics and Astronomy