# The Role of Apolipoprotein A-V in Chylomicron Metabolism

> **NIH NIH F31** · UNIVERSITY OF CINCINNATI · 2021 · $40,195

## Abstract

The Role of Apolipoprotein A-V in Chylomicron Metabolism
Cardiovascular disease, diabetes and obesity are major clinical problems worldwide, and elevated plasma
triglyceride (TG) levels constitute an independent risk factor for these chronic disorders. Discovered in 2001,
apolipoprotein A-V (apoA-V) is a protein synthesized and secreted by the liver and its levels are inversely
proportional to plasma TG levels. Compared with other apolipoproteins, such as apoA-IV and apoA-I, apoA-V
circulates at extremely low concentrations, raising the question as to how such a low circulating apolipoprotein
can exert such a profound effect on plasma TG. While apolipoproteins serve many roles in lipid metabolism, the
mechanism behind apoA-V's ability to lower plasma TG levels is not clear. Our lab was the first to report that
apoA-V regulates the production and secretion of chylomicrons (CMs) by the small intestines. We found that: 1)
apoA-V knockout (KO) mice are significantly better in the absorption and lymphatic transport of both TG and
cholesterol than WT animals; 2) apoA-V KO mice secrete more apoB48 (therefore have more CM particles since
there is one apoB48 per particle) into lymph than WT animals; 3) apoA-V is secreted into lymph during active fat
absorption associated with CMs; and 4) apoA-V is present in bile, representing a second route of apoA-V
transport, with the first being the circulation. In this proposal, we will investigate 1) the importance of apoA-
V transport to the small intestine via bile; and 2) the importance of apoA-V on CM metabolism following
its secretion from the intestine. First, we will determine whether the formation and secretion of CMs by the
small intestines is influenced by apoA-V from the circulation versus that from the bile. Second, we will determine
if and how apoA-V regulates the metabolism of CMs. Precisely, we will determine the importance of apoA-V in
CMs versus apoA-V in the circulation in the metabolism of CMs. Information from the proposed studies may
provide insight to our understanding of the inverse relationship between circulating apoA-V and plasma TG
levels. The proposed research is not only novel, but it also takes advantage of the unique conscious lymph fistula
mouse model. Training in carrying out lymph fistula mouse and various biochemical and physiological studies
will be invaluable in establishing me as a biomedical researcher in lipoprotein (especially CM) and lipid
metabolism. The proposed studies may also provide insight into the therapeutic treatment of
hypertriglyceridemia, obesity, diabetes and cardiovascular disease. Hypothesis: ApoA-V is secreted by the
liver into the bile to regulate CM formation and secretion by the gut so as not to overwhelm the metabolic
capacity of the liver; e.g. following hepatectomy. AIM 1: Since the liver is the only organ that synthesizes
and secretes apoA-V, we will determine whether the formation and secretion of CM by the gut is influenced by
apoA-V from bile versu...

## Key facts

- **NIH application ID:** 10069995
- **Project number:** 5F31DK122706-02
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Xenia Danae Davis
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $40,195
- **Award type:** 5
- **Project period:** 2019-12-02 → 2022-12-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10069995

## Citation

> US National Institutes of Health, RePORTER application 10069995, The Role of Apolipoprotein A-V in Chylomicron Metabolism (5F31DK122706-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10069995. Licensed CC0.

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