Hepatic stellate cells are an important cellular site for β-carotene conversion to retinoid.
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.
Shmarakov
Igor
I
Department of Medicine, Columbia University, New York, NY 10032, USA.
Fleshman
Matthew K
MK
D'Ambrosio
Diana N
DN
Piantedosi
Roseann
R
Riedl
Ken M
KM
Schwartz
Steven J
SJ
Curley
Robert W
RW
von Lintig
Johannes
J
Rubin
Lewis P
LP
Harrison
Earl H
EH
Blaner
William S
WS
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
D012333:RNA, Messenger; D012176:Retinoids; D019207:beta Carotene; C493359:Bco1 protein, mouse; D050559:beta-Carotene 15,15'-Monooxygenase
J Histochem Cytochem. 2004 Apr;52(4):491-9
15034000
FASEB J. 2009 Apr;23(4):1041-53
19103647
FASEB J. 2003 Jul;17(10):1304-6
12759335
FEBS Lett. 1990 Nov 12;274(1-2):89-92
2253789
J Biol Chem. 2001 Mar 2;276(9):6560-5
11092891
J Nutr. 2007 Nov;137(11):2346-50
17951468
FASEB J. 1996 Jul;10(9):940-54
8801176
Vitam Horm. 2007;75:131-59
17368315
Genomics. 2001 Mar 1;72(2):193-202
11401432
Biochem J. 2005 May 15;388(Pt 1):363-9
15628969
J Cell Biochem. 2004 May 15;92(2):414-23
15108365
J Biol Chem. 1985 Nov 5;260(25):13560-5
2997171
FASEB J. 2010 Jun;24(6):1656-66
20061533
Eur J Nutr. 2009 Aug;48(5):261-8
19533199
Int J Biochem Cell Biol. 2001 Oct;33(10):1000-12
11470233
J Lipid Res. 1997 Nov;38(11):2173-92
9392416
J Biol Chem. 2001 Aug 24;276(34):32160-8
11418584
Exp Cell Res. 1984 Jan;150(1):186-93
6420172
Hepatology. 1992 Feb;15(2):336-42
1310477
Physiol Rev. 2008 Jan;88(1):125-72
18195085
Arch Biochem Biophys. 2008 Apr 15;472(2):126-38
18295589
Science. 2001 Nov 30;294(5548):1866-70
11729302
Hepatology. 1987 Nov-Dec;7(6):1224-9
2824313
Cell Metab. 2008 Apr;7(4):302-11
18396136
J Biol Chem. 2001 Apr 27;276(17):14110-6
11278918
J Lipid Res. 1989 Oct;30(10):1545-50
2614257
Eur J Biochem. 1987 Apr 15;164(2):301-7
3569264
Lipids. 1986 Feb;21(2):164-9
3007912
J Lipid Res. 2002 Nov;43(11):1773-808
12401878
J Histochem Cytochem. 2005 Nov;53(11):1403-12
15983114
J Lipid Res. 1985 Oct;26(10):1241-51
4067418
J Biol Chem. 2007 Nov 16;282(46):33553-33561
17855355
Nat Med. 2007 Jun;13(6):695-702
17529981
J Nutr. 1999 Dec;129(12):2271-7
10573562
Biochem Biophys Res Commun. 2000 May 10;271(2):334-6
10799297
J Biol Chem. 2006 Jul 14;281(28):19327-38
16672231
Gastroenterology. 2001 Jul;121(1):91-100
11438497
Physiol Rev. 1991 Oct;71(4):951-90
1924551
J Nutr. 1989 Jan;119(1):105-8
2643691