Vitamin A and lipid metabolism: relationship between hepatic stellate cells (HSCs) and adipocytes

Abstract

Vitamin A or retinol plays a major role in the regulation of cellular homeostasis. Retinyl palmitate remains the main chemical form of vitamin A storage and is mainly located in hepatic stellate cells (HSCs) in lipid droplets resembling those found in adipose cells. White adipose tissue (WAT), is essentially involved in the regulation of lipid metabolism, through its role in lipid storage, and might also be considered as a vitamin A storage and metabolism site. WAT contains all the intracellular equipment for vitamin A metabolism and signaling pathways which allows retinol to be metabolized into retinoic acid, known to control genomic expression in WAT. The description of molecular mechanisms involved in the activation of HSCs and the differentiation of preadipocytes reveal similar cellular and molecular mechanisms. Indeed HSCs and adipocytes share a common expression of key transcription factors like PPAR-γ and RXR known to influence perilipin expression, which play fundamental roles in lipid droplet metabolism. Both cells are also sources of important endocrine signaling secretions influencing the expression of these transcription factors. The morphological and functional characteristics of HSCs and adipocytes, including the metabolism of vitamin A and other lipids and their related signaling pathways, are summarized and compared in this review. We highlight the complexity of the interrelationship between lipids and vitamin A metabolism and the role of the complex communication existing between HSCs and WAT in diseases such as non-alcoholic fatty liver disease which is the hepatic manifestation of the metabolic syndrome.

Vitamin A enrichment: Caution with encapsulation strategies used for food applications

“…New areas of research are now emerging because of vitamin A interferences with other nuclear receptors involved in the signaling pathways of vitamins, hormones and/or nutrients. For example, a lot of current data concern the interactions of vitamin A with lipid signaling pathways (see Bairras et al, 2010;Beaven et al, 2011;Bonet, Ribot, Felipe, & Palou, 2003;Redonnet et al, 2008;Sauvant et al, 2011;She, Xiong, Hazra, & Tsukamoto, 2005). As a result of these investigations, recent studies strongly suggest that vitamin A could be involved, directly or indirectly (via RXR and/or RAR) in multiple pathological diseases, such as Alzheimer's (Mingaud et al, 2008), plurimetabolic syndrome and its hepatic complications such as Non-Alcoholic Steato-Hepatitis (NASH) (for review see Sauvant et al, 2011), obesity (Bairras et al, 2010;Redonnet et al, 2008) and the therapeutic role of all-trans-retinoic acid (ATRA) in the treatment of some cancers such as promyelocytic leukemia (Chomienne et al, 1989;Fenaux & Degos, 2000) and the therapeutic role of 13-cis RA in the treatment of some skin, head, and neck cancers.…”

Vitamin A supply to mothers and children

“…After a generally efficient absorption, involving chylomicrons and the lymphatic route, vitamin A is metabolized and stored under esterified form in the liver and in the adipose tissue [5]. These organs ensure the close regulation of the level of circulating retinol in serum at around 2 mmol/l.…”

Differential Lipotoxic Effects of Palmitate and Oleate in Activated Human Hepatic Stellate Cells and Epithelial Hepatoma Cells

“…Nonactivated stellate cells proliferate slowly and synthesize a limited amount of extracellular matrix. Their predominant function is to regulate vitamin A homeostasis through its storage as retinyl palmitate in cytoplasmic lipid droplets, and its mobilization and transport into plasma [31,32]. However, in response to liver injury, including exposure to excess lipids, lipid metabolites, and inflammatory cytokines released by hepatocytes and Kupffer cells in the setting of NAFLD, stellate cells become activated [33,34].…”