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

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.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Food Science & Human Nutrition

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2024

Author dc:creator

• Catalan Monroy, Walter Alexis

Contributors dc:contributor

• Amengual Terrasa, Jaume
• Erdman, John W
• Hasnin, Saima

• Fatty Liver
• Carotenoids
• Cardiovascular Disease

Statement dc:rights

• Copyright 2024 Walter Alexis Catalan Monroy

Language dc:language

en, eng

Handle dc:identifier

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

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F127509