Establishing the role of vitamin a production in hepatocytes in cardiometabolic diseases

Catalan Monroy, Walter Alexis

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https://hdl.handle.net/2142/127509 Copy

Description

Title

Establishing the role of vitamin a production in hepatocytes in cardiometabolic diseases

Author(s)

Catalan Monroy, Walter Alexis

Issue Date

2024-12-12

Director of Research (if dissertation) or Advisor (if thesis)

Amengual Terrasa, Jaume

Committee Member(s)

• Erdman, John W
• Hasnin, Saima

Department of Study

Food Science & Human Nutrition

Discipline

Food Science & Human Nutrition

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

M.S.

Degree Level

Thesis

Keyword(s)

• Fatty liver
• carotenoids
• cardiovascular disease

Abstract

The conversion of dietary β-carotene to vitamin A by the β-carotene oxygenase 1 (BCO1) mitigates cardiometabolic diseases such as atherosclerosis and liver steatosis. Followed by adipocytes, hepatocytes are the major reservoirs of β-carotene in the body. Hepatocytes also participate in vitamin A homeostasis and are key players in regulating energy metabolism. This study aims to examine the cardiometabolic effects of β-carotene in hepatocytes as a vitamin A precursor. To test the impact of hepatocyte-specific vitamin A production, we fed β-carotene to BCO1-deficient (Bco1-/-) mice and injected them with a hepatocyte-specific adeno-associated vector encoding BCO1 (L-AAV-BCO1). To study atherosclerosis, we cross-bred Bco1-/- mice with the atheroprone low-density lipoprotein receptor-deficient (Ldlr-/-) mice to generate Bco1-/-Ldlr-/- mice. We fed Bco1-/-Ldlr-/- mice a Western diet (WD) supplemented with β-carotene (WD-β-carotene) and injected them with either L-AAV-BCO1 or an L-AAV encoding green-fluorescent protein (L-AAV-GFP) as control. To study the effect of hepatocyte-specific vitamin A production in the context of liver steatosis, we fed Bco1-/- mice a high-fat, high-sucrose (HFHS) diet supplemented with β-carotene (HFHS-β-carotene). L-AAV-BCO1 infusions increased vitamin A stores and retinoic acid signaling in Bco1-/- mice fed β-carotene, mitigated atherosclerosis progression, monocytosis, and monocyte recruitment to the lesion in Bco1-/- Ldlr-/- mice fed WD with β-carotene. L-AAV-BCO1 treatment in Bco1-/- Ldlr-/- mice fed a WD-β-carotene and Bco1-/- mice fed HFHS-β-carotene resulted in an overall reduction of hepatic lipid content, increased hepatic fatty acid oxidation, and reduced lipogenesis in comparison to age, and sex-matched controls injected with L-AAV-GFP. The effects of L-AAV-BCO1 were absent in mice fed HFHS with no β-carotene, implicating vitamin A formation in the cardiometabolic effects of L-AAV-BCO1 treatments. Our findings suggest that targeting hepatic β-carotene stores in hepatocytes to produce vitamin A is a viable strategy to mitigate the development of cardiometabolic diseases.

Graduation Semester

2024-12

Type of Resource

Thesis

Handle URL

https://hdl.handle.net/2142/127509

Copyright and License Information

Copyright 2024 Walter Alexis Catalan Monroy

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