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Researchers produce proteins that reduce excess levels of triglycerides

Wed, 03/25/2020 - 05:51
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Excess levels of triglycerides - The more APOA5 you have the faster the triglyceride is removed

Researchers Mark Castleberry, a doctoral student, and professor Sean Davidson, both in the UC College of Medicine, have found a way to produce Apolipoprotein A5 (APOA 5) protein in the laboratory. It plays an important role in metabolising and clearing excess levels of triglycerides from the bloodstream. Their findings, ‘Functional recombinant apolipoprotein A5 that is stable at high concentrations at physiological pH’, were published in the Journal of Lipid Research.

"We are really interested in understanding triglycerides because hypertriglyceridemia - too much fat in your blood - is a big factor leading to cardiovascular disease, diabetes, obesity and other health concerns," explains Davidson, who holds appointments in UC's departments of Pathology and Laboratory Medicine and Molecular Genetics, Biochemistry and Microbiology. "When you have a lot of fat that is hanging around in your circulation it's important to clear as much of it out as soon as possible."

Mark Castleberry and Sean Davidson (Credit: Colleen Kelley/University of Cincinnati)
Mark Castleberry and Sean Davidson (Credit: Colleen Kelley/University of Cincinnati)

“APOA5 is highly involved in how fast triglycerides get taken out of your circulation. The more APOA5 you have the faster the triglyceride is removed,” said Davidson. “Everybody agrees it is an important protein but scientists don't know much about its structure or how it does what it does. If we could figure out how it works we could come up with a drug that uses the same mechanism or trigger it to work better."

The researchers inserted a human gene coded by DNA into bacteria genetically engineered to produce human proteins. Once those proteins were produced they were removed from the host and purified for use in studies at the lab bench and in mouse models.

"We can quickly make a much greater amount of this protein using bacterial production than if we tried to isolate it from blood in humans," Castleberry, who is studying in the UC Department of Molecular Genetics, Biochemistry and Microbiology, and first author of the paper. "The mice in this study were basically fed a large bowl of fat and triglycerides. We could analyse their blood after we fed them and observe the level of fat change as they digested the meal. We were able to give our protein to the mice that had that fatty meal and rapidly clear the triglycerides that would have accumulated in their blood."