"This varied capability to store fat among genetically identical cells is a well-observed but poorly understood phenomenon," Cheng said
The researchers determined that these differences in fat storage depend not on fat-gene expression but on variations in a cascade of events within an "insulin-signaling pathway." The pathway enables cells to take up glucose from the blood.
"Only one small variation at the beginning of the cascade can lead to a drastic variation in fat storage at the end of the cascade," Cheng said.
The researchers conducted "single cell profiling" using a combination of imaging techniques to precisely compare fat storage in cloned cells having the same fat genes expressed.
Single cell profiling allows researchers to precisely compare the inner workings of individual cells, whereas the conventional analytical approach in biochemistry measures entire populations of cells and then provides data representing an average.
"In this case, we don't want an average. We need to find out what causes fat storage at the single-cell level so that we can compare one cell to another, " Le said. "By profiling multiple events in single cells, we found that variability in fat storage is due to varied rates of insulin processing among cells."
The cell culture used in the research contains cloned mice fibroblast cells.
"This particular type of cell culture has been used to study the molecular control of obesity for the past 35 years," Cheng said. "Researchers have observed tremendous variability in how much fat is stored in cells with identical genes, but no one really knows why. Our findings have shed some light on this phenomenon."
The researchers used a specialized imaging method called coherent anti-Stokes Raman scattering, or CARS, combined with other techniques, including flow cytometry and fluorescence microscopy.
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