Hepatic retinoid stores are required for normal liver regeneration

Shmarakov, Igor O.; Jiang, Hongfeng; Yang, Kryscilla Jian Zhang; Goldberg, Ira J.; Blaner, William S.

doi:10.1194/jlr.m029801

Cited by 27 publications

(24 citation statements)

References 57 publications

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“…Possibly HSC lipid-droplet retinoid stores are needed to buffer against disease development, but this hypothesis remains to be established. In this regard, recently published data indicate that HSC retinoid stores do not protect against CCl 4 -induced fi brosis in mice ( 126 ) but that they are required to ensure optimal liver regeneration in response to a 70% partial hepatectomy ( 127 ).…”

Section: Hepatic Storagementioning

confidence: 99%

Retinol and retinyl esters: biochemistry and physiology

O’Byrne

Blaner

2013

Journal of Lipid Research

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The different retinoid forms present within the body (see Fig. 1 ) are generated by and large through modifi cations to the terminal polar end group of the molecule. Retinol and retinyl esters are the most abundant retinoid forms present in the body. All-trans -retinol is by defi nition vitamin A. When a fatty acyl group is esterifi ed to the hydroxyl terminus of retinol, a storage form of retinol, the retinyl ester, is formed. The most abundant retinyl esters present in the body are those of palmitic acid, oleic acid, stearic acid, and linoleic acid ( 6, 7 ). Although retinyl acetate can be found in supplements to foods and vitamin formulations, only long-chain acyl groups are esterifi ed to retinol by animals. Retinyl esters have no known biological activity aside from retinol storage and for serving as the substrate for the formation of the visual chromophore 11-cis -retinal, which must be formed from all-trans -retinyl ester through linked hydrolysis and isomerization reactions catalyzed by the enzyme RPE65 ( 3,4,8,9 ). Retinol is a transport form and a precursor form, which is enzymatically activated to retinoic acid via a two-step oxidation process. The primary role of retinal is in the eye where 11-cis -retinal is needed for visual pigment formation. In tissues, retinal serves as an intermediate in the synthesis of retinoic acid from retinol ( 6, 7 ). The literature also suggests a direct role for retinal in adipose tissue, where it was shown to inhibit adipogenesis and suppress peroxisome proliferator-activated receptor-␥ (PPAR ␥ ) and retinoid X receptor (RXR) responses in cell culture models and in mouse models fed high-fat diets ( 10 ).Abstract By defi nition, a vitamin is a substance that must be obtained regularly from the diet. Vitamin A must be acquired from the diet, but unlike most vitamins, it can also be stored within the body in relatively high levels. For humans living in developed nations or animals living in present-day vivariums, stored vitamin A concentrations can become relatively high, reaching levels that can protect against the adverse effects of insuffi cient vitamin A dietary intake for six months, or even much longer. The ability to accumulate vitamin A stores lessens the need for routinely consuming vitamin A in the diet, and this provides a selective advantage to the organism. The molecular processes that underlie this selective advantage include effi cient mechanisms to acquire vitamin A from the diet, effi cient and overlapping mechanisms for the transport of vitamin A in the circulation, a specifi c mechanism allowing for vitamin A storage, and a mechanism for mobilizing vitamin A from these stores in response to tissue needs. These processes are considered in this review. Since the identifi cation of fat-soluble A a century ago ( 1 ), retinoids (vitamin A and its natural and synthetic analogs) have been the most extensively studied of the fatsoluble vitamins. This research has identifi ed essential roles for retinoids in many different aspects of mammalian physiology, includ...

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Section: Hepatic Storagementioning

confidence: 99%

Retinol and retinyl esters: biochemistry and physiology

O’Byrne

Blaner

2013

Journal of Lipid Research

Self Cite

312

250

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“…This may result from high levels of free circulating retinoids, increased retinoid signaling, induction of the retinoic acid responsive genes Cyp26a1, RARb, and p21, and subsequent p21-mediated inhibition of hepatocyte proliferation [87]. This observation was unexpected because dietary retinoid intake in humans and retinoic acid administration to cultured cancer cells or to mice subjected to experimental cancer models have often been found to provide chemoprotection against cancer development [81,89]. To assess whether this hepatic response in the total absence of retinoid stores is specific to DEN or whether it can be more generalized to other hepatic toxins, Shmarakov et al [81] undertook studies of thioacetamide (TAA)-induced hepatic toxicity in LRAT −/− mice.…”

Section: Hscs As Regulators Of Hepatocellular Damagementioning

confidence: 90%

“…This observation was unexpected because dietary retinoid intake in humans and retinoic acid administration to cultured cancer cells or to mice subjected to experimental cancer models have often been found to provide chemoprotection against cancer development [81,89]. To assess whether this hepatic response in the total absence of retinoid stores is specific to DEN or whether it can be more generalized to other hepatic toxins, Shmarakov et al [81] undertook studies of thioacetamide (TAA)-induced hepatic toxicity in LRAT −/− mice. While wild type mice developed liver injury (evidenced by focal necrotic areas and increases in serum ALT activity and myeloperoxidase activity in hepatic parenchyma) within 48 h of TAA-treatment, remarkably none of these TAA-induced effects were observed in LRAT −/− mice [81].…”

Section: Hscs As Regulators Of Hepatocellular Damagementioning

confidence: 94%

“…To assess whether this hepatic response in the total absence of retinoid stores is specific to DEN or whether it can be more generalized to other hepatic toxins, Shmarakov et al [81] undertook studies of thioacetamide (TAA)-induced hepatic toxicity in LRAT −/− mice. While wild type mice developed liver injury (evidenced by focal necrotic areas and increases in serum ALT activity and myeloperoxidase activity in hepatic parenchyma) within 48 h of TAA-treatment, remarkably none of these TAA-induced effects were observed in LRAT −/− mice [81]. Loss of hepatoprotection in LRAT −/− mice administered retinyl acetate over 48 h suggested that TAA-dependent hepatotoxicity depends on availability of retinoid metabolites.…”

Section: Hscs As Regulators Of Hepatocellular Damagementioning

confidence: 99%

“…Retinoic acid, the major transcriptionally active retinoid species, regulates more than 500 genes [80,81]. The all-trans-and 9-cis-isomers of retinoic acid regulate transcription upon binding to one of their six cognate nuclear receptors, the retinoic acid receptors (RARα, RARβ, and RARγ) and the retinoid X receptors (RXRα, RXRβ, and RXRγ) [82,83].…”

Section: Hscs As Regulators Of Hepatocellular Damagementioning

confidence: 99%

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