Hepatic metabolism of retinoids and disease associations

Abstract

The liver is the most important tissue site in the body for uptake of postprandial retinoid, as well as for retinoid storage. Within the liver, both hepatocytes and hepatic stellate cells (HSCs) are importantly involved in retinoid metabolism. Hepatocytes play an indispensable role in uptake and processing of dietary retinoid into the liver, and in synthesis and secretion of retinol-binding protein (RBP), which is required for mobilizing hepatic retinoid stores. HSCs are the central cellular site for retinoid storage in the healthy animal, accounting for as much as 50–60% of the total retinoid present in the entire body. The liver is also an important target organ for retinoid actions. Retinoic acid is synthesized in the liver and can interact with retinoid receptors which control expression of a large number of genes involved in hepatic processes. Altered retinoid metabolism and the accompanying dysregulation of retinoid signaling in the liver contribute to hepatic disease. This is related to HSCs, which contribute significantly to the development of hepatic disease when they undergo a process of cellular activation. HSC activation results in the loss of HSC retinoid stores and changes in extracellular matrix deposition leading to the onset of liver fibrosis. An association between hepatic disease progression and decreased hepatic retinoid storage has been demonstrated. In this review article, we summarize the essential role of the liver in retinoid metabolism and consider briefly associations between hepatic retinoid metabolism and disease.

Liver immune responses to inflammatory stimuli in a diet-induced obesity model of zebrafish

“…Retinoids are anti-inflammatory molecules that promote cellular differentiation. The liver is the most important site for retinoid storage, and its deregulation is associated with hepatic fibrosis and hepatocarcinoma (Shirakami et al 2012). Interestingly, an important group of these most regulated genes in the obese liver are primarily characterized for their neuronal related function, including mpzl2, cbln4, vax1, znf512b, and tuba1al.…”

“…Moreover, retinoids are anti-inflammatory molecules that promote cellular differentiation. The liver is the most important site for retinoid storage, and deregulation of this storage is associated with hepatic fibrosis and hepatocarcinoma (Shirakami et al 2012). …”

Role of antioxidants in electro catalysis of cytochrome P450 3A4

“…Далее, ретиналь необратимо окисляется до транс-ретиноевой кислоты ретиналь дегидрогеназой и далее окисляется семейством цитохромов Р450, (в основном CYP26) в тканях печени [29,30]. Эти данные свидетельствуют об отсутствии субстратных свойств витамина А по отношению к цитохромам Р450.…”

Cytochrome P450 system components and nitric oxide synthase activity in mouse liver under conditions of retinoid stores absence

“…70% из этих ретиноидов сохраняются в липидных каплях звёздчатых клеток печени (клетках Ито) [25], тогда как гепатоциты играют важную роль в поглощении и превращении ретиноидов в печени, синтезе и секреции ретинол-связывающего белка (РСБ), необходимого для мобилизации ретиноидов, клетки Ито является центральным сайтом хранения ретиноидов. Вероятно, снижение n-гидроксилазной активности CYP в печени нокаутных мышей (рис.…”

“…Вероятно, снижение n-гидроксилазной активности CYP в печени нокаутных мышей (рис. 1А), обусловлено низким уровнем ретиноевой кислоты, вследствие отсутствия запасов витамина А, поскольку реакции гидроксилирования, происходящие с участием семейств изоформ CYP1A, CYP3A, CYP4A, CYP1В, CYP2C, CYP2S, индуцируются, в основном, ретиноидами [25].…”