Cellular Insulin-Processing Abilities Linked to Obesity

In a surprising turn of events, a team of researchers from the Purdue University has learned that it may not be genes that determine a person's risk of developing obesity, but actually the way in which that person's cells process insulin. During the studies, identical cells were proven to accumulate more or less fat, depending on slight variations in the ways they processed insulin. When the investigators finally figure out how this biological mechanism works, they could potentially create novel ways of treating, or even preventing, obesity.

“Insights from our study also will be important for understanding the precise roles of insulin in obesity or Type II diabetes, and to the design of effective intervention strategies,” Purdue University Weldon School of Biomedical Engineering Ji-Xin Cheng, who is also an assistant professor in the Department of Chemistry, explained.

He added that the team noticed drastic changes in the amount of fat cells could retain when insulin was processed very fast. According to the study results, the faster insulin is processed, the more fat is accumulated inside each cell.

“This work supports an emerging viewpoint that not all biological information in cells is encoded in the genetic blueprint. We found that the variability in fat storage is dependent on how 3T3-L1 cells process insulin, a hormone secreted by the pancreas after meals to trigger the uptake of glucose from the blood into the liver, muscle or fat cells,” National Institutes of Health (NIH) postdoctoral fellow Thuc T. Le, who has collaborated with Cheng for the new research, added. A paper detailing their finds appeared in the Public Library of Science's online journal PLoS ONE.

The experts also learned that it was not genes that were responsible for fattier cells, but certain irregularities that occurred in the “cascade” processes that took place along insulin-signaling pathways. “This varied capability to store fat among genetically identical cells is a well-observed but poorly understood phenomenon. 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 shared. By using a scientific observation tool known as single cell profiling, the team was able to determine the differences that occurred between individual cells in the 3T3-L1 cell line process.

“This particular type of cell culture has been used to study the molecular control of obesity for the past 35 years. 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,” Cheng concluded.