Date of Completion

8-24-2017

Embargo Period

8-29-2017

Advisors

Alison Kohan, PhD, Christopher Blesso, PhD, Maria-Luz Fernandez, PhD, FAHA, Ji-Young Lee, PhD, FAHA,

Field of Study

Nutritional Science

Degree

Master of Science

Open Access

Open Access

Abstract

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.

Major Advisor

Alison Kohan, PhD

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