Scientists had previously identified the genes responsible for synthesizing fat within cells. But the genes governing the next step--packaging the fat inside a layer of phospholipids and proteins to form lipid droplets—have long been sought, and for good reason.
“Storing fat in lipid droplets appears crucially important for enabling cells to use fat as an energy source,” says Dr. David Silver, assistant professor of biochemistry at Einstein and senior author of the article. “From yeast to humans, partitioning fat into droplets is a universal feature among animals. And in humans, of course, acquiring excessive amounts of these fat droplets in our fat tissue leads to obesity.”
Dr. Silver and his colleagues identified two genes that are crucial for packaging fat into lipid droplets. They called the genes FIT1 and FIT2 (for Fat-Inducing Transcripts 1 and 2). Both genes code for proteins that are more than 200 amino acids in length, and the two genes are 50 percent similar to each other. The amino acid sequences of the FIT proteins do not resemble any other known proteins found in any species, indicating that the FIT genes comprise a novel gene family.
The researchers conducted several different experiments to confirm the roles of FIT1 and FIT2 in fat storage. In one experiment, they overexpressed both FIT1 and FIT2 genes (i.e., inserted extra copies of them) in human cells. While the rate of fat synthesis stayed the same in both “overexpressed” and control cells, the number of lipid droplets in the “overexpressed” cells increased dramatically, between four- and six-fold.
Using a different tactic to evaluate FIT function, the researchers next “knocked down” FIT2 in mouse fat cells (FIT1 is not expressed in these cells). Their reasoning: If FIT2 is indeed essential for lipid droplet formation, then suppressing FIT2 expression should abolish lipid-droplet accumulation. Examination of these fat cells for lipid droplets revealed that cells with suppressed FIT2 expression had a drastic reduction in lipid droplets.
Finally, the researchers carried out a similar FIT2 “knock down” experiment in a whole animal—the zebrafish. Zebrafish eggs were injected with a segment of DNA designed to interfere with FIT2 expression. Then, to induce lipid droplet formation in zebrafish larvae (where it is localized mainly in the liver and intestine), free-swimming six-day-old larvae were fed a high-fat diet for six hours. Although the larvae had exhibited normal feeding behavior, examination of their livers and intestines revealed a near-absence of lipid droplets.
“These lines of evidence supported our conclusion that FIT genes are necessary for the accumulation of lipid droplets in cells,” says Dr. Silver. “Now that we’ve identified the genes and the proteins they code for, it should be possible to develop drugs that can regulate their expression or activity. Such drugs could prove extremely valuable, not only for treating the main result of excess lipid droplet accumulation—obesity--but for alleviating the serious disorders that arise from obesity including type 2 diabetes and heart disease.”
Karen Gardner | EurekAlert!
During HIV infection, antibody can block B cells from fighting pathogens
14.08.2018 | NIH/National Institute of Allergy and Infectious Diseases
First study on physical properties of giant cancer cells may inform new treatments
14.08.2018 | Brown University
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur
What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...
The quality of materials often depends on the manufacturing process. In casting and welding, for example, the rate at which melts solidify and the resulting microstructure of the alloy is important. With metallic foams as well, it depends on exactly how the foaming process takes place. To understand these processes fully requires fast sensing capability. The fastest 3D tomographic images to date have now been achieved at the BESSY II X-ray source operated by the Helmholtz-Zentrum Berlin.
Dr. Francisco Garcia-Moreno and his team have designed a turntable that rotates ultra-stably about its axis at a constant rotational speed. This really depends...
08.08.2018 | Event News
27.07.2018 | Event News
25.07.2018 | Event News
14.08.2018 | Information Technology
14.08.2018 | Life Sciences
14.08.2018 | Life Sciences