Retinol Esterification by DGAT1 Is Essential for Retinoid Homeostasis in Murine Skin

Shih, Michelle; Kane, Maureen A.; Zhou, Ping; Yen, Chi Liang Eric; Streeper, Ryan S.; Napoli, Joseph L.; Farese, Robert V.

doi:10.1074/jbc.m807503200

Cited by 90 publications

(101 citation statements)

References 50 publications

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“…This observation suggests that a third enzyme is able to esterify retinol in the intestine when very high levels of retinol have been consumed. Studying Dgat1 -defi cient mice, Farese and colleagues independently established that DGAT1 can infl uence retinoid homeostasis in the skin of mice ( 44 ). Thus, in at least two mouse tissues, intestine and skin, DGAT1 acts physiologically in catalyzing retinyl ester formation.…”

Section: Intestinal Absorptionmentioning

confidence: 99%

“…LRAT is capable of esterifying retinol when it is bound to one of the cellular retinolbinding proteins (CRBPI, CRBPII, or CRBPIII), whereas ARAT is not ( 34 ). Several published studies have established that one of the two enzymes responsible for the fi nal step in triglyceride synthesis, diacylglycerol acyltransferase 1 (DGAT1), possesses ARAT activity in vitro ( 28,(43)(44)(45)(46). DGAT1, when expressed in vitro, will catalyze retinyl ester formation using nonprotein-bound retinol as a substrate, but it is unable to catalyze retinyl ester formation when the retinol is supplied bound to CRBPI or CRBPII ( 28 ).…”

Section: Downloaded Frommentioning

confidence: 99%

See 1 more Smart Citation

Retinol and retinyl esters: biochemistry and physiology

O’Byrne

Blaner

2013

Journal of Lipid Research

312

250

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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: Intestinal Absorptionmentioning

confidence: 99%

Section: Downloaded Frommentioning

confidence: 99%

Retinol and retinyl esters: biochemistry and physiology

O’Byrne

Blaner

2013

Journal of Lipid Research

312

250

View full text Add to dashboard Cite

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“…Shih et al ( 25 ), through study of Dgat1 Ϫ / Ϫ mice, demonstrated that DGAT1 acts physiologically in catalyzing RE synthesis in mouse skin. Dgat1 is highly expressed in the liver, where it has been shown to have a role in hepatic triglyceride synthesis ( 19,20,26 ).…”

Section: Lc/ms/ms Analysis Of Ramentioning

confidence: 99%

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

Wongsiriroj

Jiang

Piantedosi

et al. 2014

Journal of Lipid Research

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“…When dietary retinol is abundant, DGAT1 deficiency results in elevated levels of RA in skin and cyclical hair loss [88]. Deletion of DGAT1 specifically in the epidermis causes alopecia.…”

Section: Development Of Skin In Retinoid Signaling Deficient Micementioning

confidence: 99%

“…Deletion of DGAT1 specifically in the epidermis causes alopecia. DGAT1 functions as an ARAT in the skin, where it acts to maintain retinoid homeostasis and modulate RA signaling [88].…”

Section: Development Of Skin In Retinoid Signaling Deficient Micementioning

confidence: 99%

Retinoic Acid-Induced Epidermal Transdifferentiation in Skin

Akimoto

Miyaji

Morimoto-Kamata

et al. 2014

JDB

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Retinoids function as important regulatory signaling molecules during development, acting in cellular growth and differentiation both during embryogenesis and in the adult animal. In 1953, Fell and Mellanby first found that excess vitamin A can induce transdifferentiation of chick embryonic epidermis to a mucous epithelium (Fell, H.B.; Mellanby, E. Metaplasia produced in cultures of chick ectoderm by high vitamin A. J. Physiol. 1953, 119, 470-488). However, the molecular mechanism of this transdifferentiation process was unknown for a long time. Recent studies demonstrated that Gbx1, a divergent homeobox gene, is one of the target genes of all-trans retinoic acid (ATRA) for this transdifferentiation. Furthermore, it was found that ATRA can induce the epidermal transdifferentiation into a mucosal OPEN ACCESS J. Dev. Biol. 2014, 2 159 epithelium in mammalian embryonic skin, as well as in chick embryonic skin. In the mammalian embryonic skin, the co-expression of Tgm2 and Gbx1 in the epidermis and an increase in TGF-β2 expression elicited by ATRA in the dermis are required for the mucosal transdifferentiation, which occurs through epithelial-mesenchymal interaction. Not only does retinoic acid (RA) play an important role in mucosal transdifferentiation, periderm desquamation, and barrier formation in the developing mammalian skin, but it is also involved in hair follicle downgrowth and bending by its effect on the Wnt/β-catenin pathway and on members of the Runx, Fox, and Sox transcription factor families.

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Retinol Esterification by DGAT1 Is Essential for Retinoid Homeostasis in Murine Skin

Cited by 90 publications

References 50 publications

Retinol and retinyl esters: biochemistry and physiology

Retinol and retinyl esters: biochemistry and physiology

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

Retinoic Acid-Induced Epidermal Transdifferentiation in Skin

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