Genetic dissection of retinoid esterification and accumulation in the liver and adipose tissue

Wongsiriroj, Nuttaporn; Jiang, Hongfeng; Piantedosi, Roseann; Yang, Kryscilla Jian Zhang; Kluwe, Johannes; Schwabe, Robert F.; Ginsberg, Henry N.; Goldberg, Ira J.; Blaner, William S.

doi:10.1194/jlr.m043844

Cited by 39 publications

(38 citation statements)

References 62 publications

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“…To measure cellular retinol levels, highly sensitive ultraperformance liquid chromatography coupled with mass spectrometry (LC-MS) was used (22). For all-trans RA (atRA) extraction, samples were subjected to a two-step acid-base extraction as described before (23), with minor modifications.…”

Section: Methodsmentioning

confidence: 99%

Retinoic Acid Mediates Visceral-Specific Adipogenic Defects of Human Adipose-Derived Stem Cells

et al. 2016

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Increased visceral fat, rather than subcutaneous fat, during the onset of obesity is associated with a higher risk of developing metabolic diseases. The inherent adipogenic properties of human adipose-derived stem cells (ASCs) from visceral depots are compromised compared with those of ASCs from subcutaneous depots, but little is known about the underlying mechanisms. Using ontological analysis of global gene expression studies, we demonstrate that many genes involved in retinoic acid (RA) synthesis or regulated by RA are differentially expressed in human tissues and ASCs from subcutaneous and visceral fat. The endogenous level of RA is higher in visceral ASCs; this is associated with upregulation of the RA synthesis gene through the visceral-specific developmental factor WT1. Excessive RA-mediated activity impedes the adipogenic capability of ASCs at early but not late stages of adipogenesis, which can be reversed by antagonism of RA receptors or knockdown of WT1. Our results reveal the developmental origin of adipocytic properties and the pathophysiological contributions of visceral fat depots.

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Section: Methodsmentioning

confidence: 99%

Retinoic Acid Mediates Visceral-Specific Adipogenic Defects of Human Adipose-Derived Stem Cells

et al. 2016

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“…The liver captures retinoids from chylomicron remnants, where they undergo further conversion to retinol and other bioactive forms. A minor fraction is distributed to peripheral tissues bound to retinol binding proteins (RBPs) or albumin, but 90% of the stored vitamin A remains in the liver [11]. At the target tissues the retinaldehyde dehydrogenase enzymes (RALDHs) catalyze the rate-limiting step to local epithelial RA production (Figure 1) [12].…”

Section: Basic Molecular Biology Of Retinoidsmentioning

confidence: 99%

“…For the purpose of storage, upon entering the target tissues, retinal is esterified to a fatty acid, providing the means of concentrating retinol within the cells [11]. The degradation of retinoids in the body is also highly regulated and is catalyzed by cytochrome P-450 dependent enzymes in a hydroxylation and a subsequent oxidation step.…”

Section: Basic Molecular Biology Of Retinoidsmentioning

confidence: 99%

Retinoids and rexinoids in cancer prevention: from laboratory to clinic

Uray

Dmitrovsky

Brown

2016

Seminars in Oncology

129

102

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Early in the age of modern medicine the consequences of vitamin A deficiency drew attention to the fundamental link between retinoid-dependent homeostatic regulation and malignant hyperproliferative diseases. The term retinoid includes a handful of endogenous and a large group of synthetic derivatives of vitamin A. These multifunctional lipid-soluble compounds directly regulate target genes of specific biological functions and critical signaling pathways to orchestrate complex functions from vision to development, metabolism and inflammation. Many of the retinoid activities on the cellular level have been well characterized and translated to the regulation of processes like differentiation and cell death, which play critical roles in the outcome of malignant transformation of tissues. In fact, retinoid-based differentiation therapy of acute promyelocytic leukemia was one of the first successful examples of molecularly targeted treatment strategies. The selectivity, high receptor binding affinity and the ability of retinoids to directly modulate gene expression programs present a distinct pharmacological opportunity for cancer treatment and prevention. However, to fully exploit their potential, the adverse effects of retinoids must be averted. In this review we provide an overview of the biology of retinoid (activated by nuclear retinoic acid receptors, RARs) and rexinoid (engaged by nuclear retinoid X receptors, RXRs) action concluded from a long line of preclinical studies, in relation to normal and transformed states of cells. We will also discuss the past and current uses of retinoids in the treatment of malignancies, the potential of rexinoids in the cancer prevention setting, both as single agents and in combinations.

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“…Retinoic acid concentrations were determined as we have previously reported (47). Penta-deuterated ATRA (ATRA-d5) was used as an internal standard and was purchased from Toronto Research Chemicals (North York, ON, Canada).…”

Section: Methodsmentioning

confidence: 99%

Cardiac dysfunction in β-carotene-15,15′-dioxygenase-deficient mice is associated with altered retinoid and lipid metabolism

Lee

Jiang

Trent

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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Genetic dissection of retinoid esterification and accumulation in the liver and adipose tissue

Cited by 39 publications

References 62 publications

Retinoic Acid Mediates Visceral-Specific Adipogenic Defects of Human Adipose-Derived Stem Cells

Retinoic Acid Mediates Visceral-Specific Adipogenic Defects of Human Adipose-Derived Stem Cells

Retinoids and rexinoids in cancer prevention: from laboratory to clinic

Cardiac dysfunction in β-carotene-15,15′-dioxygenase-deficient mice is associated with altered retinoid and lipid metabolism

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