Retinoids: Potent regulators of metabolism

Brun, Pierre‐Jacques; Yang, Kryscilla Jian Zhang; Lee, Seung‐Ah; Yuen, Jason J.; Blaner, William S.

doi:10.1002/biof.1056

Cited by 72 publications

(61 citation statements)

References 101 publications

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“…These receptors are members of the steroid/thyroid superfamily of ligand dependent nuclear transcription factors that include the receptors for steroids, thyroid hormone, and vitamin D. Following ligand activation, the receptors function as heterodimeric transcription factors and control the expression of numerous target genes by binding to specific DNA sequences termed RA response elements (RAREs). 20,21 …”

Section: Retinoidsmentioning

confidence: 99%

A role for the liver in parturition and preterm birth

Mawson¹

2016

J Transl Sci

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Neither the mechanisms of parturition nor the pathogenesis of preterm birth are well understood. Poor nutritional status has been suspected as a major causal factor, since vitamin A concentrations are low in preterm infants. However, even large enteral doses of vitamin A from birth fail to increase plasma concentrations of vitamin A or improve outcomes in preterm and/or extremely low birthweight infants. These findings suggest an underlying impairment in the secretion of vitamin A from the liver, where about 80% of the vitamin is stored. Vitamin A accumulates in the liver and breast during pregnancy in preparation for lactation. While essential in low concentration for multiple biological functions, vitamin A in higher concentration can be pro-oxidant, mutagenic, teratogenic and cytotoxic, acting as a highly surface-active, membrane-seeking and destabilizing compound. Regarding the mechanism of parturition, it is conjectured that by nine months of gestation the hepatic accumulation of vitamin A (retinol) from the liver is such that mobilization and secretion are impaired to the point where stored vitamin A compounds in the form of retinyl esters and retinoic acid begin to spill or leak into the circulation, resulting in amniotic membrane destabilization and the initiation of parturition. If, however, the accumulation and spillage of stored retinoids reaches a critical threshold prior to nine months, e.g., due to cholestatic liver disease, which is common in mothers of preterm infants, the increased retinyl esters and/or retinoic acid rupture the fetal membranes, inducing preterm birth and its complications, including retinopathy, necrotizing enterocolitis and bronchopulmonary dysplasia. Subject to testing, the model suggests that measures taken prior to and during pregnancy to improve liver function could reduce the risk of adverse birth outcomes, including preterm birth.

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Section: Retinoidsmentioning

confidence: 99%

A role for the liver in parturition and preterm birth

Mawson¹

2016

J Transl Sci

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“…Retinoids are synthetic and natural analogues of VA, and there is interest in the potential of retinoids as anti-NAFLD agents because of their favorable effects on lipid metabolism [14, 15]. Our laboratory previously demonstrated an essential role for retinoids and for retinoic acid receptor-β (RARβ) in the regulation of pancreatic endocrine function and in the pathogenesis of obesity and NAFLD [16–18].…”

Section: Introductionmentioning

confidence: 99%

A retinoic acid receptor β2 agonist reduces hepatic stellate cell activation in nonalcoholic fatty liver disease

et al. 2016

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Hepatic stellate cells (HSCs) are an important cellular target for the development of novel pharmacological therapies to prevent and treat non-alcoholic fatty liver diseases (NAFLD). Using a high fat diet (HFD) model of NAFLD, we sought to determine if synthetic selective agonists for retinoic acid receptor β2 (RARβ2) and RARγ can mitigate HSC activation and HSC relevant signaling pathways during early stages of NAFLD, before the onset of liver injury. We demonstrate that the highly selective RARβ2 agonist, AC261066, can reduce the activation of HSCs, marked by decreased HSC expression of α-smooth muscle actin (α-SMA), in mice with HFD-induced NAFLD. Livers of HFD-fed mice treated with AC261066 exhibited reduced steatosis, oxidative stress, and expression of pro-inflammatory mediators, such as tumor necrosis factor-alpha (TNFα), interleukin 1β (IL-1β), and monocyte chemotactic protein-1 (MCP-1). Kupffer cell (macrophage) expression of transforming growth factor-β1 (TGF-β1), which plays a critical role in early HSC activation, was markedly reduced in AC261066 treated, HFD-fed mice. In contrast, HFD-fed mice treated with an RARγ agonist (CD1530) showed no decreases in steatosis, HSC activation, or Kupffer cell TGF-β1 levels. In conclusion, our data demonstrate that RARβ2 is an attractive target for development of NAFLD therapies.

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“…Biologically, high concentrations of ~10 µM/L atRA reduce cell-cell and cell-matrix interactions, affect cell differentiation, and mitochondrial mass and membrane potential as tools towards its apoptotic effect (El-Metwally et al, 2005). Such retinoid receptor mediated-effects utilize modulation of rate of expression of hundreds of genes (Brun et al, 2013;Hx et al, 2014). This study as the first worldwide attempt to screen the retinoic acid parasiticidal activity against E. granulosus was based on such abilities of atRA to regulate cellular differentiation, proliferation, metabolism and apoptosis as very dynamic tools used by the ever evolving parasite.…”

Section: Discussionmentioning

confidence: 99%

Viability loss and ultrastructural changes on protoscolices of human hydatid cysts induced by retinoic acid

Yones¹,

Mahmoud²,

Othman³

et al. 2014

J. Parasitol. Vector Biol.

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Surgical removal of intact hydatid cyst is the most effective treatment for hydatid disease. Recurrence of hydatid cyst is mainly due to dissemination of protoscolices (PSCs) rich fluid during the surgical operation. Therefore, preoperative instillation of a scolicidal agent into the cyst is a common practice with adverse side effects of the used drugs. All-trans retinoic acid (atRA) is the physiological mediator of most of the functions of vitamin A, particularly as a cellular differentiation and apoptosis regulating factor. We hypothesized that instillation of atRA could provide an alternative safe scolicidal approach. We tested the scolicidal effects and ultrastructural changes imposed by atRA on human hydatid cyst PSCs in vitro. Freshly isolated hydatid cyst PSCs were subjected to atRA (at 16.7, 1.67, 0.167 µM and 16.7 nM/L). Changes in protoscolices viability (0.1% eosin exclusion) and morphology (scanning and transmission electron microscopy; SEM and TEM) were investigated. Dose-dependent PSCs death within few minutes to 7 days of exposure to atRA was observed. SEM demonstrated ultrastructural damages including rosteller disorganization, loss of hooks and distortion of hooks morphology. TEM revealed loss of the integrity of the internal tissues of PSCs, an increased vacuolization, formation of large lipid droplets in the distal cytoplasm and aberrant, rounded abnormally large sized mitochondria. atRA is a promising alternative to the available synthetic and chemical scolicidal agents. However, in vivo scolicidal activities of atRA and the possible side effects necessitate further studies.

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Retinoids: Potent regulators of metabolism

Cited by 72 publications

References 101 publications

A role for the liver in parturition and preterm birth

A role for the liver in parturition and preterm birth

A retinoic acid receptor β2 agonist reduces hepatic stellate cell activation in nonalcoholic fatty liver disease

Viability loss and ultrastructural changes on protoscolices of human hydatid cysts induced by retinoic acid

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