All-trans-retinoic acid ameliorates atherosclerosis, promotes perivascular adipose tissue browning, and increases adiponectin production in Apo-E mice

AbstractAll-trans-retinoic acid (atRA), an active metabolite of vitamin A, exerts a potential role in the prevention of cardiovascular diseases. It has been shown that atRA ameliorates atherosclerosis while the exact mechanism underlying this protection remains unknown. This study investigated the influence of atRA on insulin resistance (IR), atherosclerosis, and the process of perivascular adipose tissue (PVAT) browning. Moreover, syntheses of adiponectin, adipokine with anti-atherogenic effects, and tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine, were determined in PVAT. Apolipoprotein E-deficient mice (Apo-E) and control C57BL/6J wild-type mice were treated with atRA (5 mg/kg/day) or vehicle (corn oil) by plastic feeding tubes for 8 weeks. Long-term atRA treatment in Apo-E mice did not affect insulin resistance. AtRa administration ameliorated atherosclerosis, induced PVAT browning, and increased adiponectin production in PVAT in Apo-E mice. Furthermore, atRA increased nitric oxide (NO) level but did not affect adiponectin concentration in the aorta of Apo-E mice. These results indicate that atRA ameliorates atherosclerosis in Apo-E mice. We also observed the browning of PVAT. Besides, atRA increased the synthesis of adiponectin in PVAT and augmented NO level in the aorta in ApoE mice.

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LncRNA H19-mediated mouse cleft palate induced by all-trans retinoic acid

Human & Experimental Toxicology ◽

10.1177/0960327116651121 ◽

2016 ◽

Vol 36 (4) ◽

pp. 395-401 ◽

Cited By ~ 5

Author(s):

L Gao ◽

Y Liu ◽

Y Wen ◽

W Wu

Keyword(s):

Retinoic Acid ◽

Cleft Palate ◽

Target Gene ◽

Functional Roles ◽

New Class ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid ◽

Age Related ◽

And Control

Long noncoding RNAs (lncRNAs) are the new class of transcripts and pervasively transcribed in the genome, which have been found to play important functional roles in many tissues and organs. LncRNAs can interact with target gene to exert their functions. However, the function and mechanism of lncRNA in cleft palate (CP) development remain elusive. Here, we investigated the role of lncRNA H19 and its target gene insulin-like growth factor 2 (IGF2) in CP of mice. All-trans retinoic acid (atRA) is a well-known teratogenic effecter of CP. After establishment of the CP mouse model using atRA in vivo, we found that the rate of CP in mice was 100%. The tail lengths of fetuses in atRA-treated mice were shorter than those of control mice from embryonic day (E)12 to E17. The expression of lncRNA H19 and IGF2 were embryo age-related differences between atRNA-treated and control mice. In addition, the the relationship between lncRNA H19 and IGF2 were negative correlation in the critical period of developmental palate. These findings suggest that lncRNA H19 mediate atRA-induced CP in mice.

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Regulation of thrombomodulin expression by all-trans retinoic acid and tumor necrosis factor-alpha: differential responses in keratinocytes and endothelial cells

Blood ◽

10.1182/blood.v88.6.2043.bloodjournal8862043 ◽

1996 ◽

Vol 88 (6) ◽

pp. 2043-2049 ◽

Cited By ~ 9

Author(s):

TJ Raife ◽

EM Demetroulis ◽

SR Lentz

Keyword(s):

Endothelial Cells ◽

Retinoic Acid ◽

Tumor Necrosis Factor ◽

Tumor Necrosis Factor Alpha ◽

Tumor Necrosis ◽

Necrosis Factor Alpha ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid ◽

Factor Alpha ◽

Necrosis Factor

Thrombomodulin is a cell-surface anticoagulant glycoprotein expressed by vascular endothelial cells and epidermal keratinocytes. Thrombomodulin expression in endothelial cells is regulated by retinoic acid and tumor necrosis factor-alpha (TNF), agents that also modulate epidermal differentiation. We examined thrombomodulin function and regulation of thrombomodulin expression by all-trans retinoic acid (ATRA) and TNF in human keratinocytes and endothelial cells. Untreated keratinocytes and endothelial cells expressed thrombomodulin of comparable activity and apparent thrombin affinity. Incubation of keratinocytes with 10 mumol/L ATRA for 24 hours increased thrombomodulin activity 5.4 +/- 0.9-fold (mean +/- SE), with equivalent increases observed in thrombomodulin protein (5.5 +/- 2.1-fold) and mRNA (4.2 +/- 1.2-fold). Incubation of keratinocytes with 1.0 nmol/L TNF markedly increased expression of keratinocyte transglutaminase, but had no effect on thrombomodulin activity, protein, or mRNA. In endothelial cells, ATRA produced a small increase in thrombomodulin activity (1.9 +/- 0.1-fold), and incubation with TNF for 24 hours decreased thrombomodulin activity 83% +/- 7%. The activity profile of keratinocyte thrombomodulin exhibited a distinct maximum near 1.0 mmol/L Ca2+. These results demonstrate that keratinocyte thrombomodulin is regulated by retinoids and Ca2+, but not by TNF, and that regulation of thrombomodulin expression differs in keratinocytes and endothelial cells.

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Nuclear All-trans Retinoic Acid Receptors in Liver of Rats with Diet-induced Insulin Resistance

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.1997.tb51857.x ◽

1997 ◽

Vol 827 (1 Lipids and Sy) ◽

pp. 480-484

Author(s):

J. BRTKO ◽

E. šEBÖKOVÁ ◽

D. GAšPERÍKOVÁ ◽

I. KLIMEš ◽

S. HUDECOVÁ ◽

...

Keyword(s):

Insulin Resistance ◽

Retinoic Acid ◽

Retinoic Acid Receptors ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid

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Limited appearance of apocarotenoids is observed in plasma after consumption of tomato juices: a randomized human clinical trial

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqy177 ◽

2018 ◽

Vol 108 (4) ◽

pp. 784-792 ◽

Cited By ~ 4

Author(s):

Jessica L Cooperstone ◽

Janet A Novotny ◽

Ken M Riedl ◽

Morgan J Cichon ◽

David M Francis ◽

...

Keyword(s):

Retinoic Acid ◽

Biological Function ◽

Retinoic Acid Receptor ◽

Tomato Juice ◽

Human Clinical Trial ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid ◽

And Control ◽

Β Carotene

Abstract Background Nonvitamin A apocarotenoids occur in foods. Some function as retinoic acid receptor antagonists in vitro, though it is unclear if apocarotenoids are absorbed or accumulate to levels needed to elicit biological function. Objective The aim of this study was to quantify carotenoids and apocarotenoids (β-apo-8′-, -10′-, -12′-, and -14′-carotenal, apo-6′-, -8′-, -10′-, -12′-, and -14′-lycopenal, retinal, acycloretinal, β-apo-13-carotenone, and apo-13-lycopenone) in human plasma after controlled consumption of carotenoid-rich tomato juices. Design Healthy subjects (n = 35) consumed a low-carotenoid diet for 2 wk, then consumed 360 mL of high-β-carotene tomato juice (30.4 mg of β-carotene, 34.5 μg total β-apocarotenoids/d), high-lycopene tomato juice (42.5 mg of lycopene, 119.2 μg total apolycopenoids/d), or a carotenoid-free control (cucumber juice) per day for 4 wk. Plasma was sampled at baseline (after washout) and after 2 and 4 wk, and analyzed for carotenoids and apocarotenoids using high-pressure liquid chromatography (HPLC) and HPLC-tandem mass spectrometry, respectively. The methods used to analyze the apocarotenoids had limits of detection of ∼ 100 pmol/L. Results Apocarotenoids are present in tomato juices at 0.1–0.5% of the parent carotenoids. Plasma lycopene and β-carotene increased (P < 0.001) after consuming high-lycopene and β-carotene tomato juices, respectively, while retinol remained unchanged. β-Apo-13-carotenone was found in the blood of all subjects at every visit, although elevated (P < 0.001) after consuming β-carotene tomato juice for 4 wk (1.01 ± 0.27 nmol/L) compared with both baseline (0.37 ± 0.17 nmol/L) and control (0.46 ± 0.11 nmol/L). Apo-6′-lycopenal was detected or quantifiable in 29 subjects, while β-apo-10′- and 12′-carotenal were detected in 6 and 2 subjects, respectively. No other apolycopenoids or apocarotenoids were detected. Conclusions β-Apo-13-carotenone was the only apocarotenoid that was quantifiable in all subjects, and was elevated in those consuming high-β-carotene tomato juice. Levels were similar to previous reports of all-trans-retinoic acid. Other apocarotenoids are either poorly absorbed or rapidly metabolized or cleared, and so are absent or limited in blood. β-Apo-13-carotenone may form from vitamin A and its presence warrants further investigation. This trial was registered at clinicaltrials.gov as NCT02550483.

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