“We’re really interested in understanding triglycerides because hypertriglyceridemia – too much fat in your blood – is a major factor leading to cardiovascular disease, diabetes, obesity and other health problems,” explains Davidson, who is in appointments in holds the UC’s pathology and laboratory medicine departments and molecular genetics, biochemistry and microbiology. “When you have a lot of fat in your system, it’s important to remove as much of it as possible.”
“APOA5 is instrumental in how quickly triglycerides are cleared from your circulation,” says Davidson, who has a PhD in biochemistry. “The more APOA5 you have, the faster the triglyceride will be removed. Everyone agrees that it’s 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 develop a drug that uses the same mechanism or triggers it to work better. “
The work demonstrates UC’s commitment to research as outlined in its Next Lives Here strategic direction.
According to Castleberry, researchers inserted a human gene that was encoded by DNA in bacteria that have been genetically engineered to produce human proteins. Once these proteins were made, they were removed from the host and purified for use in bench-top studies and in mouse models.
“With the production of bacteria, we can quickly produce a much larger amount of this protein than if we were to try to isolate it from the blood in humans,” explains Castleberry. “The mice in this study were basically given a large bowl of fat and triglycerides.”
“We were able to analyze their blood after we fed them and observe the level of fat change as they digested the meal,” said Castleberry. “We were able to feed our protein to our mice that had this fatty meal and quickly get rid of the triglycerides that would have built up in their blood.”
Other co-authors on this study were Xenia Davis; Thomas Thompson, professor in the Department of Molecular Genetics, Biochemistry and Microbiology at UC; and Patrick Tso and Min Liu, both professors in the Department of Pathology and Laboratory Medicine at UC.
Reference: “Functional Recombinant Apolipoprotein A5 Stable at High Concentrations at Physiological pH” by Mark Castleberry, Xenia Davis, Min Liu, Thomas B. Thompson, Patrick Tso and W. Sean Davidson, December 12, 2019, Journal of Lipid Research .
DOI: 10.1194 / jlr.D119000103
The research was supported by a Heart, Lung, and Blood Institute of the National Institutes of Health, which funded a Castleberry PhD scholarship.