Date of Completion
Alison Kohan, PhD, Christopher Blesso, PhD, Maria-Luz Fernandez, PhD, FAHA, Ji-Young Lee, PhD, FAHA,
Field of Study
Master of Science
In the intestine, apoC-III delays chylomicron secretion, and causes a decrease in chylomicron size. Once apoC-III is in circulation, apoC-III delays triglyceride-rich remnants clearance by inhibiting lipoprotein lipase and liver low-density lipoprotein receptor. In humans, high levels of plasma apoC-III directly result in hypertriglyceridemia. ApoC-III is a critical cardiovascular risk factor, and humans expressing null mutations in apoC-III are robustly protected from cardiovascular disease. Because of its critical role in elevating plasma lipids and CVD risk, the factors that regulate apoC-III expression in the liver have been determined, and include glucose, insulin (through FoxO1), and dietary fat. Considerably less is known about the factors that regulate intestinal apoC-III. This study utilizes primary murine enteroids, Caco-2 cells, and dietary studies in wild-type mice to show that intestinal apoC-III expression does not change in response to fatty acids, glucose, or insulin administration, in contrast to hepatic apoC-III. Intestinal apoC-III is not sensitive to changes in FoxO1 expression (which is itself very low in the intestine, as is FoxO1 target IGFBP-1), nor is intestinal apoC-III responsive to western diet, a significant contrast to hepatic apoC-III stimulation during western diet. These data strongly suggest that intestinal apoC-III is not a FoxO1 target. These data support the idea that apoC-III is not regulated coordinately with hepatic apoC-III, and establishes another key aspect of apoC-III that is unique in the intestine and different from the liver.
West, Gabrielle, "Key Differences Between Hepatic and Intestinal apoC3 Regulation and Expression, and Implications for Cardiovascular Disease Risk" (2017). Master's Theses. 1135.
Alison Kohan, PhD