title: Hepatic stellate cells are an important cellular site for β-carotene conversion to retinoid.
abstract: Hepatic stellate cells (HSCs) are responsible for storing 90-95% of the retinoid present in the liver. These cells have been reported in the literature also to accumulate dietary β-carotene, but the ability of HSCs to metabolize β-carotene in situ has not been explored. To gain understanding of this, we investigated whether β-carotene-15,15'-monooxygenase (Bcmo1) and β-carotene-9',10'-monooxygenase (Bcmo2) are expressed in HSCs. Using primary HSCs and hepatocytes purified from wild type and Bcmo1-deficient mice, we establish that Bcmo1 is highly expressed in HSCs; whereas Bcmo2 is expressed primarily in hepatocytes. We also confirmed that HSCs are an important cellular site within the liver for accumulation of dietary β-carotene. Bcmo2 expression was found to be significantly elevated for livers and hepatocytes isolated from Bcmo1-deficient compared to wild type mice. This elevation in Bcmo2 expression was accompanied by a statistically significant increase in hepatic apo-12'-carotenal levels of Bcmo1-deficient mice. Although apo-10'-carotenal, like apo-12'-carotenal, was readily detectable in livers and serum from both wild type and Bcmo1-deficient mice, we were unable to detect either apo-8'- or apo-14'-carotenals in livers or serum from the two strains. We further observed that hepatic triglyceride levels were significantly elevated in livers of Bcmo1-deficient mice fed a β-carotene-containing diet compared to mice receiving no β-carotene. Collectively, our data establish that HSCs are an important cellular site for β-carotene accumulation and metabolism within the liver.
authors.affiliation: Department of Medicine, Columbia University, New York, NY 10032, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Shmarakov
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Fleshman
authors.forename: Diana N
authors.initials: DN
authors.lastname: D'Ambrosio
authors.forename: Roseann
authors.initials: R
authors.lastname: Piantedosi
authors.forename: Ken M
authors.initials: KM
authors.lastname: Riedl
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Schwartz
authors.forename: Robert W
authors.initials: RW
authors.lastname: Curley
authors.forename: Johannes
authors.initials: J
authors.lastname: von Lintig
authors.forename: Lewis P
authors.initials: LP
authors.lastname: Rubin
authors.forename: Earl H
authors.initials: EH
authors.lastname: Harrison
authors.forename: William S
authors.initials: WS
authors.lastname: Blaner
mesh_terms: D000818:Animals; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism*; D019207:beta Carotene / Q000378:metabolism*; D050559:beta-Carotene 15,15'-Monooxygenase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D012176:Retinoids; D019207:beta Carotene; C493359:Bco1 protein, mouse; D050559:beta-Carotene 15,15'-Monooxygenase
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