β-Cryptoxanthin Suppresses the Adipogenesis of 3T3-L1 Cells via RAR Activation

Abstract

SummaryWe recently reported that the oral intake of ␤ -cryptoxanthin exerted anti-obesity effects by lowering visceral fat levels. In the present study, we characterized the molecular mechanisms underlying the lipid-lowering effects of ␤ -cryptoxanthin on 3T3-L1 cells. Consistent with our previous findings, ␤ -cryptoxanthin rapidly reduced the level of intracellular lipids in 3T3-L1 cells as assessed by Oil red O staining. Using an in vitro nuclear receptor binding assay, we demonstrated the ability of ␤ -cryptoxanthin to bind to and activate members of the retinoic acid receptor (RAR) family. Accordingly, treatment of cells with LE540, an RAR antagonist, abolished the ␤ -cryptoxanthin-dependent suppression of 3T3-L1 adipogenesis, suggesting that ␤ -cryptoxanthin mediates its effects on 3T3-L1 cells via RAR activation. In addition, real-time RT-PCR analysis revealed that ␤ -cryptoxanthin down-regulates mRNA expression of PPAR ␥ , a key regulator of adipocyte differentiation, and that this inhibition was blocked by LE540 treatment. Taken together, these data indicate that RAR activation contributes to the molecular mechanism by which ␤ -cryptoxanthin prevents obesity.

Role of PPARγ in the nutritional and pharmacological actions of carotenoids

“…Combined with their results on fucoxanthin and fucoxanthinol, they suggested that carotenoids containing an allene bond and an additional hydroxyl substituent on the side group may show suppressive effects on adipocyte differentiation in 3T3L1 cells. [102][103][104]117 It should be noted that their observation is not in agreement with the results obtained by Shirakura et al using β-cryptoxanthin 101 or García-Rojas et al using lutein in a bovine adipocyte-differentiation system, in which 30 µM lutein increased PPARγ mRNA expression. 62 Perhaps the hydroxyl group at the third position of the ionone ring is also important for carotenoid effects.…”

“…Their results indicated that β-cryptoxanthin inhibited 3T3L1 adipogenesis via the downregulation of PPARγ through RAR activation. 101 Fucoxanthin is a major carotenoid present in edible seaweed, such as Undaria pinnatifida and Hizikia fusiformis. Fucoxanthin and its metabolites, fucoxanthinol and amarouciaxanthin A, inhibited the adipocyte differentiation of 3T3L1 cells through downregulation of PPARγ and C/EBPα.…”

Suppression of Sebum Production and Accumulation by <i>β</i>-Cryptoxanthin Due to the Inhibition of the Expression of Diacylglycerol Acyltransferase-1 and Perilipin in Hamster Sebocytes

“…In the present study, we found that not only intracellular lipid-droplet formation but also the gene expression and production of PLIN1 was suppressed by β-CRX in differentiated hamster sebocytes. A similar inhibition of lipid-droplet formation has been reported to be observed in β-CRX-treated mouse 3T3-L1 adipocytes [31]. Therefore, the β-CRX-inhibition of lipid-droplet formation is likely to include the transcriptional suppression of PLIN1 production in hamster sebocytes.…”

“…In addition, β-CRX is a vitamin A precursor, which is oxidatively cleaved to vitamin A by β-carotene 15,15'-dioxygenase [29], and can be stably stored in some tissue for several months [30]. Taken together with a recent report by Shirakura et al [31] where β-CRX inhibits the intracellular lipid-droplet formation in mouse 3T3-L1 adipocytes, we hypothesize that, instead of retinoids such as atRA and 13-cisRA, β-CRX is an effective candidate for acne therapy by modulating sebaceous lipogenesis. However, it is not fully understood whether β-CRX directly suppresses sebum production and accumulation in sebaceous gland cells (sebocytes) or not.…”

“…In the inflamed acne lesions resulting from comedogenesis, the expression and activation of PPARγ have been reported to be augmented and closely associated with the aggravation of acne pathology [44,45]. Shirakura et al [31] reported that β-CRX does not affect peroxisome proliferators activating receptor γ (PPARγ) activation. We have preliminarily demonstrated that β-CRX did not alter the PPARγ ligand, troglitazone-augmented production of TGs and PLIN1 production in hamster sebocytes (Sato T and Ito A, unpublished data).…”