2026-09-26T03:02:44Z https://www.ideals.illinois.edu/oai-pmh

oai:www.ideals.illinois.edu:2142/127509 2026-02-03 col_2142_5131 col_2142_14781 com_2142_5130 com_2142_687 com_2142_397

application/pdf en text Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2026-12-01 The student, Walter Catalan Monroy, accepted the attached license on 2024-12-06 at 16:13. The student, Walter Catalan Monroy, submitted this Thesis for approval on 2024-12-06 at 16:40. This Thesis was approved for publication on 2024-12-12 at 08:28. DSpace SAF Submission Ingestion Package generated from Vireo submission #21537 on 2025-03-28 at 14:57:02 Establishing the role of vitamin a production in hepatocytes in cardiometabolic diseases Catalan Monroy, Walter Alexis 2024-12-12 Amengual Terrasa, Jaume Erdman, John W Hasnin, Saima Fatty Liver Carotenoids Cardiovascular Disease eng 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. 2024-12 Thesis https://hdl.handle.net/2142/127509 Copyright 2024 Walter Alexis Catalan Monroy Food Science & Human Nutrition Food Science & Human Nutrition University of Illinois at Urbana-Champaign M.S. Thesis