21 Carotenoids as Anti-obesity Supplements
547
21.3.3 Carotenoids Regulate Gene Expression in Adipocytes
and Adipose Tissue
Several molecular mechanisms mediating the effects of carotenoids on gene expression have been described. In the case of provitamin A carotenoids, leading to retinoic
acid synthesis, retinoic acid receptors (RARs), and retinoid X receptors (RXRs)
constitute specific signaling targets. Two families of receptors mediate the effects
of retinoids (Germain et al. 2006a, b). Three subtypes of each have been described
(RARα RARβ, RARγ, RXRα, RXRβ, and RXRγ). These receptors work as liganddependent transcriptional regulators by binding specific DNA sequences [Retinoic
Acid Response Element (RARE) or Retinoid X Response Element (RXRE)] found
in the promoter region of retinoid target genes either as RAR-RXR or RXR-RXR
dimers. RARs and RXRs subtypes are found in every cell type. Furthermore, RXRs
are dimerization partners for other nuclear receptors such as peroxisome proliferatoractivated receptors (PPARs), liver X receptor (LXR), farnesoid X receptor (FXR),
pregnane X receptor (PXR), RARs, thyroid hormone receptor (TR), and vitamin D
receptor (VDR), leading to the regulation of a huge number of genes. In addition,
several other transcription factors and signaling pathways are modulated by retinoic
acid (Yasmeen et al. 2012), including PPARβ ((Berry and Noy 2009). Lycopene
(Aydemir et al. 2012) and apo-10
-lycopenoic acid (Gouranton et al. 2011) are also
able to activate RAR. Many carotenoids regulate gene expression via ubiquitous
signaling pathways such as NF-κB and MAP kinases (Rao et al. 2006; Sharoni et al.
2012), or via transcription factors involved in detoxification such as AhR, NRF2, or
PXR (Ben-Dor et al. 2005; Landrier 2012).
21.4 Carotenoids and/or Metabolites Impact Adipocyte
Biology in in Vitro Studies
The impact of some carotenoids has been documented in adipogenesis, which
could contribute to obesity management, via a limitation of lipid accumulation in
adipocytes. Most of the reported effects inhibited adipocyte differentiation (Kawada
et al. 2000) by interfering with nuclear receptors such as RAR, RXR, or PPAR.
Indeed, β-carotene inhibited adipogenesis not only through the production of β-apo14
-carotenal and repression of PPARα, PPARγ, and RXR activation (Ziouzenkova
et al. 2007), but also through the production of all-trans retinoic acid (Lobo et al.
2010). Similarly, β-cryptoxanthin suppresses adipogenesis via activation of RAR
(Shirakura et al. 2011), and astaxanthin inhibits rosiglitazone-induced adipocyte
differentiation by antagonizing transcriptional activity of PPARγ (Inoue et al. 2012).
Zeaxanthin (Liu et al. 2017) and fucoxanthin (Maeda et al. 2006; Seo et al. 2016)
exhibited anti-adipogenic effect via a down-regulation of adipogenic transcription
factors C/EBPα and PPARγ, which blunted lipid accumulation. Conversely, lycopene
(unpublished personal data) and apo-10
-lycopenoic acid (Gouranton et al. 2011)
547
21.3.3 Carotenoids Regulate Gene Expression in Adipocytes
and Adipose Tissue
Several molecular mechanisms mediating the effects of carotenoids on gene expression have been described. In the case of provitamin A carotenoids, leading to retinoic
acid synthesis, retinoic acid receptors (RARs), and retinoid X receptors (RXRs)
constitute specific signaling targets. Two families of receptors mediate the effects
of retinoids (Germain et al. 2006a, b). Three subtypes of each have been described
(RARα RARβ, RARγ, RXRα, RXRβ, and RXRγ). These receptors work as liganddependent transcriptional regulators by binding specific DNA sequences [Retinoic
Acid Response Element (RARE) or Retinoid X Response Element (RXRE)] found
in the promoter region of retinoid target genes either as RAR-RXR or RXR-RXR
dimers. RARs and RXRs subtypes are found in every cell type. Furthermore, RXRs
are dimerization partners for other nuclear receptors such as peroxisome proliferatoractivated receptors (PPARs), liver X receptor (LXR), farnesoid X receptor (FXR),
pregnane X receptor (PXR), RARs, thyroid hormone receptor (TR), and vitamin D
receptor (VDR), leading to the regulation of a huge number of genes. In addition,
several other transcription factors and signaling pathways are modulated by retinoic
acid (Yasmeen et al. 2012), including PPARβ ((Berry and Noy 2009). Lycopene
(Aydemir et al. 2012) and apo-10
-lycopenoic acid (Gouranton et al. 2011) are also
able to activate RAR. Many carotenoids regulate gene expression via ubiquitous
signaling pathways such as NF-κB and MAP kinases (Rao et al. 2006; Sharoni et al.
2012), or via transcription factors involved in detoxification such as AhR, NRF2, or
PXR (Ben-Dor et al. 2005; Landrier 2012).
21.4 Carotenoids and/or Metabolites Impact Adipocyte
Biology in in Vitro Studies
The impact of some carotenoids has been documented in adipogenesis, which
could contribute to obesity management, via a limitation of lipid accumulation in
adipocytes. Most of the reported effects inhibited adipocyte differentiation (Kawada
et al. 2000) by interfering with nuclear receptors such as RAR, RXR, or PPAR.
Indeed, β-carotene inhibited adipogenesis not only through the production of β-apo14
-carotenal and repression of PPARα, PPARγ, and RXR activation (Ziouzenkova
et al. 2007), but also through the production of all-trans retinoic acid (Lobo et al.
2010). Similarly, β-cryptoxanthin suppresses adipogenesis via activation of RAR
(Shirakura et al. 2011), and astaxanthin inhibits rosiglitazone-induced adipocyte
differentiation by antagonizing transcriptional activity of PPARγ (Inoue et al. 2012).
Zeaxanthin (Liu et al. 2017) and fucoxanthin (Maeda et al. 2006; Seo et al. 2016)
exhibited anti-adipogenic effect via a down-regulation of adipogenic transcription
factors C/EBPα and PPARγ, which blunted lipid accumulation. Conversely, lycopene
(unpublished personal data) and apo-10
-lycopenoic acid (Gouranton et al. 2011)