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Biological Chemistry

Meals Modify Proteins

Proteomics: Levels of protein acetylation may change in response to feasting or fasting

by Erika Gebel
August 12, 2011

Mouse tissues display different patterns of protein acetylation depending on whether the animal has eaten recently.
Mouse tissues display different patterns of protein acetylation depending on whether the animal has eaten recently.

After a good meal, our bodies relish burning carbohydrates; By contrast, fasting triggers them to favor using stored fats for energy. Scientists think that defects in this tightly regulated system may underlie diseases such as diabetes, but they don’t understand the molecular mechanisms at play. Now researchers report that tissues may use a particular protein modification, acetylation, to pick their energy source (J. Proteome Res., DOI: 10.1021/pr200313x).

A few tissues in the body, such as the brain, mainly run on carbohydrates. To conserve these precious sugars for the tissues that need them most, other parts of the body switch to fats as an energy source when they have gone without food for several hours.

James Bruce of the University of Washington, Seattle, thinks that acetyl coenzyme A flips this switch in our tissues. The biomolecule sits at the crossroads of the metabolic pathways that convert carbohydrates and fat into energy. Enzymes also use the coenzyme to add acetyl groups to proteins—a modification that can alter a protein’s activity. These dual roles led Bruce and coauthor Irwin Kurland of the Albert Einstein College of Medicine to hypothesize that the amount of protein acetylation changes depending on the time since our last meal, and therefore may regulate how the body uses its energy supplies.

To test their hypothesis, the researchers studied protein acetylation in mice that had just eaten and in those that hadn’t dined in 18 hours. Since different tissues have specific fuel preferences, the researchers collected tissue samples from the mice’s liver, kidney, muscle, and two types of fat tissue. They pulverized the samples, extracted the proteins, and then separated acetylated proteins from the rest using antibodies that recognized acetyl groups.

Using liquid chromatography/tandem mass spectrometry, they identified 337 acetylated proteins. They then compared acetylation levels between fasted and fed animals for 23 proteins with known metabolic functions. The comparison revealed “pretty dramatic differences” in acetylation, Bruce says, with some proteins’ acetylation levels changing by a factor of three between the two states.

When the team examined the data for each organ, they noticed that differences in acetylation levels between fed and fasted mice correlated with the tissues’ response to the hormone insulin. Liver and skeletal muscle, which respond to insulin by maximizing energy production and storage, had greater protein acetylation levels in fasted mice versus fed ones. Meanwhile, data from the kidneys, which are less sensitive to insulin than the liver and muscles, displayed the opposite pattern. Bruce next plans to study acetylation in mice with diabetes, a disease characterized by impaired insulin signaling.

“This study suggests that acetylation plays a key role in how the body responds to the diet,” saysDavid Lombard of the University of Michigan Medical School. He says it may be possible to decipher how acetylation goes awry during disease, and to make drugs that normalize acetylation. But, he cautions, “that’s far into the future.”



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