Obesity has been associated in many epidemiological and observational studies with low circulating concentrations of carotenoids [22,23]. Strong inverse correlations between body mass index (BMI) and all measured carotenoids in plasma, except lycopene, were highlighted in the CARDIA study [24]. In addition, many obesity-associated disorders, such as low-grade inflammation or insulin resistance, are also strongly inversely associated with serum carotenoid concentrations [25,26,27].

Several trials have been conducted to study how carotenoids might be used in obesity management. Most of these studies used mixtures of carotenoids and vitamins in a natural matrix, such as fruit juices or plant extracts (reviewed by Bonet et al. [28]), making interpretation of the specific contribution of carotenoids difficult. To our knowledge, only two randomized double-blind placebo-controlled clinical trials have investigated the effect of pure carotenoid or xanthophyll supplementation. Canas et al. [29] reported a decrease in BMI z-score, waist-to-height ratio and subcutaneous adipose tissue in children given a mixture of carotenoids (β-carotene, α-carotene, lutein, zeaxanthin, lycopene, astaxanthin and γ-tocopherol) for 6 months. These beneficial effects were strongly associated with an increase in plasma β-carotene concentration in children [29]. Another study used a mixture of paprika xanthophylls and carotenoids, administered for 12 weeks to healthy overweight volunteers. This supplementation reduced visceral fat area, subcutaneous fat area and total fat area, along with BMI in the treated group compared to a placebo group [30].

It has long been known that carotenoids are notably stored in adipose tissue [51,52,53,54,55]. Lycopene and β-carotene are the predominant carotenoids in human adipose tissue [53,56]. More precisely, Chung et al. identified lycopene as the most abundant carotenoid in adipose tissue (more than 1/2), followed by β-carotene (approx. 1/3 of total carotenoids), lutein + zeaxanthin, β-cryptoxanthin and α-carotene [54].

Total carotenoid concentration appears to be site-specific, with abdomen concentration higher than in the buttocks or thigh [54]. Adipose tissue concentrations of carotenoids are similar in men and women [54]. Interestingly, plasma levels of most carotenoids are inversely correlated to fat mass and to both general and central adiposity [54,57], suggesting that during obesity, carotenoids are sequestered in adipose tissue. Conversely, weight loss is associated with an increase in lutein and zeaxanthin serum concentration [58]. In the case of β-carotene, it is noteworthy that even if its adipose tissue concentration is lower in obese people, the total pool of β-carotene is similar in obese and non-obese when taking into account total fat mass [59].

BCO1, involved in centric cleavage of carotenoids and β-carotene 9′, 10′-dioxygenase (BCO2), involved in eccentric cleavage of carotenoids, are expressed in adipocytes [71], raising the possibility that carotenoid cleavage products, including retinal, derivatives and apocarotenoids, could be found in adipocytes [31,32,72]. In agreement, retinal [73] and free retinol have been identified in the adipocyte fraction of adipose tissue [74]. Several isomers of retinol, including all-trans, 9-cis and 13-cis isomers, were also quantified in white adipose tissue [74,75,76], together with several isomers of retinoic acid, except for 9-cis retinoic acid [75,77,78]. Adipocytes express BCO1 and BCO2, together with the enzymes necessary for vitamin A metabolism, suggesting that part of the effect of provitamin A carotenoids is mediated via vitamin A production. This topic will not be dealt with here; the reader is referred to the excellent review of Dr. Blaner [50].

Besides these retinoids, β-10′-apocarotenal has been identified in adipose tissue [32]. It is highly probable that other apocarotenoids are produced in adipose tissue, but their function in adipocyte biology needs further research.

Several molecular mechanisms mediating the effects of carotenoids on gene expression have been described and may be related to the impact of carotenoids on adipocyte biology. In the case of provitamin A carotenoids, leading to retinoic acid synthesis, RARs and retinoid X receptors (RXRs), they constitute specific signaling targets. Two families of receptors mediate the effects of retinoids [79,80]. Three subtypes of each have been described (RARα RARβ, RARγ, RXRα, RXRβ and RXRγ). These receptors work as ligand-dependent 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. RAR and RXR subtypes are found in every cell type. Furthermore, RXRs are dimerization partners for other nuclear receptors such as peroxisome proliferator activated receptors (PPARs), liver X receptor (LXR), farnesoid X receptor (FXR), pregnane X receptor (PXR), RARs, thyroid hormone receptor (TR) and vitamin D receptor (VDR), which are involved in the regulation of a huge number of genes. In addition, several other transcription factors and signaling pathways are modulated by retinoic acid [81], including PPARβ ([82]. Lycopene [83] and apo-10′-lycopenoic acid [84] are also able to activate RAR. Many carotenoids regulate gene expression via ubiquitous signaling pathways such as nuclear factor-kappa B (NF-κB) and mitogen activated proteins (MAP) kinases [85,86], or via transcription factors involved in detoxification such as aryl hydrocarbon receptor (AhR), nuclear factor erythroid-2-related factor 2 (NRF2) or PXR [87,88].