Retinoids and nuclear retinoid receptors in white and brown adipose tissues: physiopathologic aspects

Abstract

Vitamin A, ingested either as retinol or β-carotene from animal- or plant-derived foods respectively, is a nutrient essential for many biological functions such as embryonic development, vision, immune response, tissue remodeling, and metabolism. Its main active metabolite is all trans-retinoic acid (atRA), which regulates gene expression through the activation of α, β, and γ isotypes of the nuclear atRA receptor (RAR). More recently, retinol derivatives were also shown to control the RAR activity, enlightening the interplay between vitamin A metabolism and RAR-mediated transcriptional control. The white and brown adipose tissues regulate the energy homeostasis by providing dynamic fatty acid storing and oxidizing capacities to the organism, in connection with the other fatty acid-consuming tissues. This concerted interorgan response to fatty acid fluxes is orchestrated, in part, by the endocrine activity of the adipose tissue depots. The adipose tissues are also sites for synthesizing and storing vitamin A derivatives, which will act as hormonal cues or intracellularly to regulate essential aspects of adipocyte biology. As agents that prevent adipocyte differentiation hence, expected to decrease fat mass, and inducers of uncoupling protein expression, thus, favoring energy expenditure, retinoids have prompted many investigations to decipher their roles in adipose tissue pathophysiology, which are summarized in this review.

Plasma Levels of Retinol Binding Protein 4 Relate to Large VLDL and Small LDL Particles in Subjects with and without Type 2 Diabetes

“…While the current study was primarily focused on RBP4, our findings with respect to retinol levels are also relevant. Retinol is the circulating form of vitamin A that is locally (in tissues) converted to retinoic acids (such as all-trans retinoic acid and 9-cis retinoic acid) that activate transcription factors (Retinoic Acid Receptor (RAR) and Retinoic X Receptor (RXR)) [35,36]. Retinol and retinoic acids simulate hepatic RBP4 secretion and enhance de novo lipogenesis in the liver [34].…”

Adipose‐Specific Expression, Developmental and Nutritional Regulation of the Gene‐Encoding Retinol‐Binding Protein 7 in Pigs

“…Because fat cell fraction contains mostly mature adipocytes, but not preadipocytes that are precipitated as stromal vascular fraction, RBP7 may significantly be expressed in mature adipocytes. Given that adipose tissue is one of the major reservoirs of retinol (Flajollet et al, ; Frey and Vogel, ) and RBP7 expression is high in mature adipocyte‐containing fraction, RBP7 may contribute to solubilize retinol potentially in a mature adipocyte‐specific manner. Developmental expression patterns further indicate an increased expression of RBP7 in the late stage of adipogenic differentiation (day 9) in vitro and an abundant expression in an adult age (120‐day‐old) in vivo .…”

“…Among RBP, RBP7 was identified as a protein abundantly produced by adipocytes across species (Ahn et al, , ; Tsutsumi et al, ). As de novo lipogenesis mainly occurs in adipose tissue in the case of pigs (Gondret et al, ; Mildner and Clarke, ) and adipose tissue is one of the major reservoirs for retinol and its metabolites (Flajollet et al, ; Frey and Vogel, ), analyses of expression patterns of RBP7 in adipose tissue as a RBP is essential to understand adipose development and lipid metabolism in pigs.…”

Modern possibilities of using systemic retinoids in dermatological practice (review of international literature)

“…Известно, что транспортный цитоплазменный белок, перехвативший ретинол, определяет дальнейшую активность ретинола [5,6]. Основная часть комплексов с ретинолом доставляется к ядерной мембране, где перехватывается рецепторами RAR (α-, β-или γ-изотипами ядерного рецептора) [6,7]. Под действием ре тинола активируются различные факторы транс крипции, ретинол разрушается белками цитохромов (CYP26A1), а рецептор RAR инактивируется (фосфорилируется) или деградирует в протеосомах [1].…”