Dietary lycopene downregulates carotenoid 15,15'-monooxygenase and PPAR-gamma in selected rat tissues.
In vitro studies have suggested that lycopene is an efficient substrate for carotenoid 9'10'-monooxygenase II (CMO2) but an inhibitor of carotenoid 15,15'-monooxygenase I (CMO1). The objectives of this study were to clone the rat CMO2 gene, determine whether feeding lycopene for different lengths of time (3-37 d) altered the expression of genes related to carotenoid cleavage [CMO1, CMO2 and peroxisomal proliferator-activated receptor gamma (PPAR-gamma)] or increased the activity of selected phase I and phase II detoxification enzymes in rat tissues. The cloned rat CMO2 gene was 92 and 82% homologous to the mouse and human CMO2 nucleotide sequence, respectively. The relative abundance of CMO1, CMO2, and PPAR-gamma were differentially expressed among rat tissues. CMO1 and PPAR-gamma expression were decreased in the kidney and adrenal with lycopene intake (P < 0.05), whereas CMO2 expression was reduced only in the kidney. Lycopene did not alter hepatic phase I activity, but hepatic quinone reductase activity increased after 3 and 7 d of lycopene feeding (P < 0.05). Lycopene intake decreased a PPAR-gamma target gene, fatty acid binding protein 3 (FABP3), in the kidney and adrenal (P < 0.05). Thus, these data show that although the intake of 0.25 g lycopene/kg diet does not induce hepatic P450 detoxification enzymes, lycopene feeding alters CMO1, PPAR-gamma, and FABP3 mRNA expression in selected rat tissues with a moderate effect on kidney CMO2 expression. These data suggest that lycopene may play an important role in the modulation of beta-carotene, retinoid, and/or lipid metabolism.
Zaripheh
Susan
S
Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801, USA.
Nara
Takayuki Y
TY
Nakamura
Manabu T
MT
Erdman
John W
JW
D000311:Adrenal Glands / Q000737:chemistry; D000818:Animals; D002338:Carotenoids / Q000008:administration & dosage*; D003001:Cloning, Molecular; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004032:Diet; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D000077276:Lycopene; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D050559:beta-Carotene 15,15'-Monooxygenase / Q000235:genetics*
C509948:FABP3 protein, rat; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D047495:PPAR gamma; D012333:RNA, Messenger; D002338:Carotenoids; D003577:Cytochrome P-450 Enzyme System; D050559:beta-Carotene 15,15'-Monooxygenase; D016660:NAD(P)H Dehydrogenase (Quinone); D000077276:Lycopene