Findings on Fat Cell Metabolism

A new study shows simple sugars are not the only favored nutrient of fat cells.

authors Cindy Sanders

A recent study out of the University of California, San Diego uncovered new insights into what nutrients fat cells metabolize in order to make fatty acids.

 an assistant professor of bioengineering in the Jacobs School of Engineering at UCSD and senior author of the study that was published online in the Nov. 16, 2015 issue of Nature Chemical Biology – said a better understanding of how fat cells develop, change, consume and metabolize their surrounding nutrients could help researchers find new approaches to treating a number of diseases.

“This study highlights how specific tissues in our bodies use particular nutrients,” he explained. “By understanding fat cell metabolism at the molecular level, we are laying the groundwork for further research to identify better drug targets for treating diabetes and obesity.”

The research team discovered that as fat cells develop, they change the types of nutrients they metabolize to produce fat and energy. In the pre-adipocyte state, which is the precursor to fat cells, glucose is the meal of preference to grow and make energy. However, as the cells mature into actual fat cells, the team found they not only metabolize simple sugars but also the more complex branched-chain amino acids, a small set of the essential amino acids for humans.

The team induced pre-adipocytes to differentiate into fat cells and cultured the cells in a media containing nutrients enriched with carbon-13 isoptopes, which are a form of carbon atoms used as metabolic tracers in cells, animals and people. By doing this, the research team could see what carbon-based nutrients the cells metabolized and what they produced at different stages of the cell differentiation process.

Their findings are important in showing fat cells play a role in regulating the body’s levels of branched-chain amino acids, which typically are elevated in individuals who are obese or diabetic.

“We quantitatively showed that this branch-chain amino acid pathway was almost equivalent to the contribution of sugar or carbohydrate to fat production,” Metallo said. “We used metabolic tracers and mass spectrometry-based metabolomics to track or trace the carbon in different nutrients to quantitatively determine where it went in the adipocytes. By visualizing the biochemistry in that way, we could quantify how amino acids, or proteins, contribute to fat production.”

He added, “The importance of this study is that it shows branched-chain amino acids are highly metabolized by normally functioning adipocytes.” A working hypothesis, then, is that higher accumulation of branched-chain amino acids occurs when there are irregularities in fat cell metabolism.

While this first step toward understanding how amino acids are accumulating in the blood of those with obesity and diabetes is important, the next step is to figure out how and why the metabolic pathways become impaired. “This gives us a pathway to understand and look at its function … or dysfunction … in detail,” Metallo said. He added, “We have a couple of different lines of investigation to determine what might cause dysfunction of this pathway in adipose tissue in diabetics.”

Metallo also noted that studies such as this one are significant because they have the power to change the questions being asked. Is someone obese or diabetic because they eat too much and move too little, because they are not burning correctly at the cellular level, or some combination of factors? “Knowing that answer can change treatment approaches,” he pointed out.


Full Paper: “Branched-chain Amino Acid Catabolism Fuels Adipocyte Differentiation and Lipogenesis”

Metallo Lab at UCSD

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