title: Beta,beta-carotene decreases peroxisome proliferator receptor gamma activity and reduces lipid storage capacity of adipocytes in a beta,beta-carotene oxygenase 1-dependent manner.
abstract: Increasing evidence has been provided for a connection between retinoid metabolism and the activity of peroxisome proliferator receptors (Ppars) in the control of body fat reserves. Two different precursors for retinoids exist in the diet as preformed vitamin A (all-trans-retinol) and provitamin A (beta,beta-carotene). For retinoid production, beta,beta-carotene is converted to retinaldehyde by beta,beta-carotene monooxygenase 1 (Bcmo1). Previous analysis showed that Bcmo1 knock-out mice develop dyslipidemia and are more susceptible to diet-induced obesity. However, the role of Bcmo1 for adipocyte retinoid metabolism has yet not been well defined. Here, we showed that Bcmo1 mRNA and protein expression are induced during adipogenesis in NIH 3T3-L1 cells. In mature adipocytes, beta,beta-carotene but not all-trans-retinol was metabolized to retinoic acid (RA). RA decreased the expression of Ppar gamma and CCAAT/enhancer-binding protein alpha, key lipogenic transcription factors, and reduced the lipid content of mature adipocytes. This process was inhibited by the retinoic acid receptor antagonist LE450, showing that it involves canonical retinoid signaling. Accordingly, gavage of beta,beta-carotene but not all-trans-retinol induced retinoid signaling and decreased Ppar gamma expression in white adipose tissue of vitamin A-deficient mice. Our study identifies beta,beta-carotene as a critical physiological precursor for RA production in adipocytes and implicates provitamin A as a dietary regulator of body fat reserves.
authors.affiliation: Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Glenn P
authors.initials: GP
authors.lastname: Lobo
authors.forename: Jaume
authors.initials: J
authors.lastname: Amengual
authors.forename: Hua Nan M
authors.initials: HN
authors.lastname: Li
authors.forename: Marcin
authors.initials: M
authors.lastname: Golczak
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Bonet
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Palczewski
authors.forename: Johannes
authors.initials: J
authors.lastname: von Lintig
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D004032:Diet; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects*; D051379:Mice; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012176:Retinoids / Q000378:metabolism; D019207:beta Carotene / Q000378:metabolism / Q000494:pharmacology*; D050559:beta-Carotene 15,15'-Monooxygenase / Q000235:genetics / Q000378:metabolism*
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D047495:PPAR gamma; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D019207:beta Carotene; C493359:Bco1 protein, mouse; D050559:beta-Carotene 15,15'-Monooxygenase