Adipose tissue plays a major role in retinoic acid-mediated metabolic homoeostasis

Retinoids, especially all-trans retinoic acid (RA), have been shown to inhibit the differentiation of preadipose cells. In the present study, the expression of retinoic acid receptors (RAR alpha, beta and gamma) and retinoid X receptors (RXR alpha, beta and gamma) was examined by Northern blot analysis in rat adipose tissue and mouse 3T3-L1 adipose cells. The adipose tissue and/or 3T3-L1 cells expressed mRNAs for a number of nuclear retinoid receptors, including RAR alpha, beta and gamma, and RXR alpha, beta and gamma. RAR alpha, RAR gamma, RXR alpha and RXR beta mRNAs were abundant in adipose tissue and 3T3-L1 cells. RXR gamma mRNA was detected in adipose tissue but not in 3T3-L1 cells. Treatment of 3T3-L1 cells with 1 microM RA led to a 4-5-fold increase in the RAR gamma mRNA level, but only a trace amount of RAR beta mRNA was detected. RAR gamma mRNA expression was rapidly (within 2 h) induced by physiological concentrations of RA in a dose-dependent manner. The response of RAR gamma mRNA expression to RA was reversible; rapid disappearance of RAR gamma mRNA occurred on RA removal. In addition, the induction of RAR gamma expression did not require de novo protein synthesis, but was completely abolished by an inhibitor of RNA synthesis. Using RAR gamma 1 and gamma 2 isoform-specific probes, the patterns of RAR gamma 1 and gamma 2 mRNA expression in 3T3-L1 cells in the presence and absence of RA were examined. RAR gamma 1 mRNA was detected in 3T3-L1 cells but was not affected by RA treatment; however, RAR gamma 2 mRNA was strongly induced by RA.

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Retinoic acid and vitamin D(3) powerfully inhibit in vitro leptin secretion by human adipose tissue

Journal of Endocrinology ◽

10.1677/joe.0.1700425 ◽

2001 ◽

Vol 170 (2) ◽

pp. 425-431 ◽

Cited By ~ 77

Author(s):

C Menendez ◽

M Lage ◽

R Peino ◽

R Baldelli ◽

P Concheiro ◽

...

Keyword(s):

Vitamin D ◽

Adipose Tissue ◽

Retinoic Acid ◽

Energy Homeostasis ◽

Human Adipose Tissue ◽

Tissue Samples ◽

Omental Adipose Tissue ◽

Vitamin D 3 ◽

Gender Based

Leptin, the product of the ob gene, is secreted into the circulation by white adipose tissue; its major role being to participate in the regulation of energy homeostasis. Plasma leptin levels are mainly determined by the relative adiposity of the subject; however, the great dispersion of values for any given body mass index and the noteworthy gender-based differences indicate that other factors are operating. Steroid hormones actively participate in the regulation of leptin secretion; however, non-steroid nuclear hormones have either not been studied or have provided contradictory results. In order to understand the role of hormones of the non-steroid superfamily such as 3,5,3'-tri-iodothyronine (T(3)), vitamin D(3) and retinoic acid (RA) in the control of leptin secretion, in the present work doses of 10(-9), 10(-8) and 10(-7) M of these compounds have been studied on in vitro leptin secretion. The organ culture was performed with omental adipose tissue samples from healthy donors (n=28). T(3) was devoid of effect at any dose studied, while an inhibition of leptin secretion was observed with 9-cis-RA (slight) and all-trans-RA (potent). Interestingly, vitamin D(3) exerted a powerfully inhibitory role at the doses studied, and its action was synergistic with all-trans-RA. In conclusion, in vitro leptin secretion by human adipose tissue is negatively controlled by either RA or vitamin D(3). The clinical significance of leptin regulation by this superfamily of nuclear receptors remains to be ascertained.

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Nutrigenomic regulation of adipose tissue development — role of retinoic acid: A review

Meat Science ◽

10.1016/j.meatsci.2016.04.003 ◽

2016 ◽

Vol 120 ◽

pp. 100-106 ◽

Cited By ~ 31

Author(s):

Bo Wang ◽

Qiyuan Yang ◽

Corrine L. Harris ◽

Mark L. Nelson ◽

Jan R. Busboom ◽

...

Keyword(s):

Adipose Tissue ◽

Retinoic Acid ◽

Tissue Development ◽

Adipose Tissue Development

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Both retinoic-acid-receptor- and retinoid-X-receptor-dependent signalling pathways mediate the induction of the brown-adipose-tissue-uncoupling-protein-1 gene by retinoids

Biochemical Journal ◽

10.1042/0264-6021:3450091 ◽

2000 ◽

Vol 345 (1) ◽

pp. 91 ◽

Cited By ~ 13

Author(s):

Rosa ALVAREZ ◽

MaLuz CHECA ◽

Sonia BRUN ◽

Octavi VIÑAS ◽

Teresa MAMPEL ◽

...

Keyword(s):

Adipose Tissue ◽

Retinoic Acid ◽

Brown Adipose Tissue ◽

Retinoic Acid Receptor ◽

Uncoupling Protein ◽

Retinoid X Receptor ◽

Signalling Pathways ◽

Uncoupling Protein 1 ◽

Acid Receptor ◽

Brown Adipose

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Lipocalin 2 regulates retinoic acid-induced activation of beige adipocytes

Journal of Molecular Endocrinology ◽

10.1530/jme-18-0017 ◽

2018 ◽

Vol 61 (3) ◽

pp. 115-126 ◽

Cited By ~ 2

Author(s):

Jessica A Deis ◽

Hong Guo ◽

Yingjie Wu ◽

Chengyu Liu ◽

David A Bernlohr ◽

...

Keyword(s):

Adipose Tissue ◽

Retinoic Acid ◽

Uncoupling Protein ◽

Oxidative Capacity ◽

Mitogen Activated Protein Kinase ◽

Peroxisome Proliferator ◽

Lipocalin 2 ◽

Peroxisome Proliferator Activated Receptor ◽

Brown Adipose ◽

Beige Adipocytes

Lipocalin-2 (LCN2) has been previously characterized as an adipokine regulating thermogenic activation of brown adipose tissue and retinoic acid (RA)-induced thermogenesis in mice. The objective of this study was to explore the role and mechanism for LCN2 in the recruitment and retinoic acid-induced activation of brown-like or ‘beige’ adipocytes. We found LCN2 deficiency reduces key markers of thermogenesis including uncoupling protein-1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) in inguinal white adipose tissue (iWAT) and inguinal adipocytes derived from Lcn2 −/− mice. Lcn2 −/− inguinal adipocytes have attenuated insulin-induced upregulation of thermogenic gene expression and p38 mitogen-activated protein kinase (p38MAPK) signaling pathway activation. This is accompanied by a lower basal and maximal oxidative capacity in Lcn2 −/− inguinal adipocytes, indicating mitochondrial dysfunction. Recombinant Lcn2 was able to restore insulin-induced p38MAPK phosphorylation in both WT and Lcn2 −/− inguinal adipocytes. Rosiglitazone treatment during differentiation of Lcn2 −/− adipocytes is able to recruit beige adipocytes at a normal level, however, further activation of beige adipocytes by insulin and RA is impaired in the absence of LCN2. Further, the synergistic effect of insulin and RA on UCP1 and PGC-1α expression is markedly reduced in Lcn2 −/− inguinal adipocytes. Most intriguingly, LCN2 and the retinoic acid receptor-alpha (RAR-α) are concurrently translocated to the plasma membrane of adipocytes in response to insulin, and this insulin-induced RAR-α translocation is absent in adipocytes deficient in LCN2. Our data suggest a novel LCN2-mediated pathway by which RA and insulin synergistically regulates activation of beige adipocytes via a non-genomic pathway of RA action.

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Repeated Retinoic Acid Treatments Modulate Adipose Tissue Development of Neonatal Rats Reared by Mothers Consuming a High Fat Diet

Current Developments in Nutrition ◽

10.1093/cdn/nzaa041_035 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 131-131

Author(s):

Libo Tan ◽

Hui Wang ◽

Yanqi Zhang

Keyword(s):

Adipose Tissue ◽

Retinoic Acid ◽

High Fat Diet ◽

Serum Triglyceride ◽

Neonatal Rats ◽

Sprague Dawley ◽

High Fat ◽

Serum Samples ◽

Significant Difference ◽

Metabolic Conditions

Abstract Objectives Retinoic acid (RA), the active metabolite of vitamin A, has been shown to be a regulator of adipose tissue (AT) development in adult models. The aim of the study was to assess the effects of repeated RA treatments on body weight (BW) gain, AT development, and metabolic conditions of neonatal rats reared by mothers consuming a high-fat diet (HFD). Methods Five Sprague-Dawley rats arrived on their second day of gestation and were randomized to either a normal-fat diet (NFD = 25% fat; n = 2) or a HFD (50% fat; n = 3) both with a marginal level of VA at 0.35 mg/kg. Half of the pups delivered by mothers in HFD cohort received oral RA treatments. Specifically, on postnatal day 5 (P5) and P8, respectively, n = 12 pups in HFD cohort received an oral RA dose at 4 μg/g BW (HFD + RA group). Remaining pups in HFD cohort (n = 12; HFD group) and pups in NFD cohort (n = 12; NFD group) both received oil as placebo. Six hours after the dose administration on P8, n = 4 pups/group were euthanized with blood, visceral white AT (WAT), and brown AT (BAT) collected. On P11 and P14, remaining pups in NFD, HFD, and HFD + RA group (n = 8/group) received a dose of oil, oil, and RA, respectively. Six hours after the administration on P14, n = 4 pups/group were sacrificed. On P17 and P20, remaining pups in each group (n = 4) received their respective treatment and were euthanized six hours afterwards on P20. Serum samples from P14 and P20 sacrifice were analyzed for concentrations of glucose, insulin, lipids, adipokines, and inflammatory markers. Results At P8 and P14, no significant difference in BW gain, WAT mass, and BAT mass of pups was noted among groups. At P20, all three measures were significantly (P < 0.05) higher in the HFD group than in the NFD group; the measures were significantly decreased in the HFD + RA group compared to the HFD group. At P20, serum adiponectin and leptin concentrations were both significantly higher in the HFD than in the NFD group; RA treatment significantly reduced the concentrations of both. The pattern of changes in serum leptin was also observed at P14. At both P14 and P20, serum triglyceride was found to be significantly higher in pups receiving RA treatment. Conclusions Repeated RA treatments exerted a regulatory role on the AT metabolism and development of neonatal offspring to mothers consuming a HFD, as evidenced by reduced BW gain and AT mass as well as modulation of adipokines. Funding Sources NIH.

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