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!
Scientists unlock ability to generate new sensory hair cells
22.02.2017 | Brigham and Women's Hospital
New insights into the information processing of motor neurons
22.02.2017 | Max Planck Florida Institute for Neuroscience
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
22.02.2017 | Power and Electrical Engineering
22.02.2017 | Life Sciences
22.02.2017 | Physics and Astronomy