In order to evaluate the expression of nuclear receptors at the peripheral level in obese subjects, messenger RNA (mRNA) levels of different isoforms of retinoic acid receptor (RAR), triiodothyronine (TR), and peroxisome proliferator-activated receptor (PPAR) were determined and compared in peripheral mononuclear blood cells (PBMC) and subcutaneous white adipose tissue (SWAT). Twelve lean subjects and 68 obese subjects divided into weight gain (WG), weight-stable (WS), and weight loss (WL) groups were studied. Nuclear receptor mRNA levels were assessed in PBMC and SWAT using a quantitative real-time reverse transcription polymerase chain reaction method. mRNA levels of RARγ were significantly lower in PBMC of obese subjects (WG −19%, WS −30%, and WL −24.7%) as in SWAT of WG (−50%). Lower mRNA levels of TRβ were observed in PBMC and SWAT of WG (−50.7% and −28%, respectively) just as for TRα in PBMC of WG (−19%). In contrast, retinoid X receptors α (RXRα) and RARα mRNA levels were higher in PBMC of obese subjects (+53% and +54.5% in WG, +56% and +67% in WS, and +68% and +49.7% in WL, respectively), while expression of RXRα was lower in SWAT of WG (−24.5%). As for PPARγ, its mRNA level was significantly higher in PBMC of WG subjects (+34%) while its expression was not modified in SWAT, contrary to the PPARγ2 isoform which was significantly higher. These data show that in both adipose tissue and blood compartment of obese subjects, expressions of RARγ and TRβ were downregulated. Thus, we suggest that the expression in PBMC of obese subjects may constitute new cellular indicators of nuclear receptor retinoid and thyroid status.


Similar content being viewed by others
Explore related subjects
Discover the latest articles and news from researchers in related subjects, suggested using machine learning.References
Bairras C, Menard L, Redonnet A, Ferrand C, Delage B, Noel-Suberville C, Atgie C, Higueret P (2005) Effect of vitamin A content in cafeteria diet on the expression of nuclear receptors in rat subcutaneous adipose tissue. J Physiol Biochem 61:353–361
Ballow M, Wang X, Xiang S, Allen C (2003) Expression and regulation of nuclear retinoic acid receptors in human lymphoid cells. J Clin Immunol 23:46–54
Chambon P (1996) A decade of molecular biology of retinoic acid receptors. Faseb J 10:940–954
Chawla A, Lazar MA (1994) Peroxisome proliferator and retinoid signaling pathways co-regulate preadipocyte phenotype and survival. Proc Natl Acad Sci U S A 91:1786–1790
De Urquiza AM, Liu S, Sjoberg M, Zetterstrom RH, Griffiths W, Sjovall J, Perlmann T (2000) Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain. Science 290:2140–2144
Delage B, Bairras C, Buaud B, Pallet V, Cassand P (2005) A high-fat diet generates alterations in nuclear receptor expression: prevention by vitamin A and links with cyclooxygenase-2 and beta-catenin. Int J Cancer 116:839–846
Feart C, Pallet V, Boucheron C, Higueret D, Alfos S, Letenneur L, Dartigues JF, Higueret P (2005) Aging affects the retinoic acid and the triiodothyronine nuclear receptor mRNA expression in human peripheral blood mononuclear cells. Eur J Endocrinol 152:449–458
Feart C, Vallortigara J, Higueret D, Gatta B, Tabarin A, Enderlin V, Higueret P, Pallet V (2005) Decreased expression of retinoid nuclear receptor (RAR alpha and RAR gamma) mRNA determined by real-time quantitative RT-PCR in peripheral blood mononuclear cells of hypothyroid patients. J Mol Endocrinol 34:849–858
Goyenechea E, Parra D, Crujeiras AB, Abete I, Martinez JA (2009) A nutrigenomic inflammation-related PBMC-based approach to predict the weight-loss regain in obese subjects. Ann Nutr Metab 54:43–51
Grover GJ, Mellstrom K, Ye L, Malm J, Li YL, Bladh LG, Sleph PG, Smith MA, George R, Vennstrom B, Mookhtiar K, Horvath R, Speelman J, Egan D, Baxter JD (2003) Selective thyroid hormone receptor-beta activation: a strategy for reduction of weight, cholesterol, and lipoprotein (a) with reduced cardiovascular liability. Proc Natl Acad Sci U S A 100:10067–10072
Gudas LJ, Sporn MB, Roberts AB (1994) Cellular biology and biochemistry of the retinoids. In: Goodman DS (ed) The retinoids: biology, chemistry and medicine. Raven Press, New York, pp 443–520
Henry RR, Wiest-Kent TA, Scheaffer L, Kolterman OG, Olefsky JM (1986) Metabolic consequences of very-low-calorie diet therapy in obese non-insulin-dependent diabetic and nondiabetic subjects. Diabetes 35:155–164
Ishaq M, Fan M, Natarajan V (2000) Accumulation of RXR alpha during activation of cycling human T lymphocytes: modulation of RXRE transactivation function by mitogen-activated protein kinase pathways. J Immunol 165:4217–4225
Jiang C, Ting AT, Seed B (1998) PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391:82–86
Kamei Y, Kawada T, Kazuki R, Sugimoto E (1993) Retinoic acid receptor gamma 2 gene expression is up-regulated by retinoic acid in 3T3-L1 preadipocytes. Biochem J 293:807–812
Kawada T, Kamei Y, Fujita A, Hida Y, Takahashi N, Sugimoto E, Fushiki T (2000) Carotenoids and retinoids as suppressors on adipocyte differentiation via nuclear receptors. Biofactors 13:103–109
Leclercq M, Bourgeay-Causse M (1981) A simple, reliable fast method: simultaneous proportioning of retinol and serum tocopherol by high performance liquid chromatography. Revue Institut Pasteur Lyon 14:475–496
Maeyama K, Emi M, Tachibana M (2005) Nuclear receptors as targets for drug development: peroxisome proliferator-activated receptor gamma in mast cells: its roles in proliferation and differentiation. J Pharmacol Sci 97:190–194
Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM (1995) The nuclear receptor superfamily: the second decade. Cell 83:835–839
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419
Metzger D, Imai T, Jiang M, Takukawa R, Desvergne B, Wahli W, Chambon P (2005) Functional role of RXRs and PPARgamma in mature adipocytes. Prostaglandins Leukot Essent Fatty Acids 73:51–58
Mukherjee R, Jow L, Croston GE, Paterniti JR Jr (1997) Identification, characterization, and tissue distribution of human peroxisome proliferator-activated receptor (PPAR) isoforms PPARgamma2 versus PPARgamma1 and activation with retinoid X receptor agonists and antagonists. J Biol Chem 272:8071–8076
Perez-Echarri N, Noel-Suberville C, Redonnet A, Higueret P, Martinez JA, Moreno-Aliaga MJ (2007) Role of adipogenic and thermogenic genes in susceptibility or resistance to develop diet-induced obesity in rats. J Physiol Biochem 63:317–327
Redonnet A, Bonilla S, Noel-Suberville C, Pallet V, Dabadie H, Gin H, Higueret P (2002) Relationship between peroxisome proliferator-activated receptor gamma and retinoic acid receptor alpha gene expression in obese human adipose tissue. Int J Obes Relat Metab Disord 26:920–927
Redonnet A, Ferrand C, Bairras C, Higueret P, Noel-Suberville C, Cassand P, Atgie C (2008) Synergic effect of vitamin A and high-fat diet in adipose tissue development and nuclear receptor expression in young rats. Br J Nutr 100:722–730
Redonnet A, Groubet R, Noel-Suberville C, Bonilla S, Martinez A, Higueret P (2001) Exposure to an obesity-inducing diet early affects the pattern of expression of peroxisome proliferator, retinoic acid, and triiodothyronine nuclear receptors in the rat. Metabolism 50:1161–1167
Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK (1998) The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 391:79–82
Safonova I, Darimont C, Amri EZ, Grimaldi P, Ailhaud G, Reichert U, Shroot B (1994) Retinoids are positive effectors of adipose cell differentiation. Mol Cell Endocrinol 104:201–211
Sewter C, Blows F, Considine R, Vidal-Puig A, O'Rahilly S (2002) Differential effects of adiposity on peroxisomal proliferator-activated receptor gamma1 and gamma2 messenger ribonucleic acid expression in human adipocytes. J Clin Endocrinol Metab 87:4203–4207
Shaw N, Elholm M, Noy N (2003) Retinoic acid is a high affinity selective ligand for the peroxisome proliferator-activated receptor beta/delta. J Biol Chem 278:41589–41592
Szabova L, Macejova D, Dvorcakova M, Mostbock S, Blazickova S, Zorad S, Walrand S, Cardinault N, Vasson MP, Rock E, Brtko J (2003) Expression of nuclear retinoic acid receptor in peripheral blood mononuclear cells (PBMC) of healthy subjects. Life Sci 72:831–836
Vidal-Puig A, Jimenez-Linan M, Lowell BB, Hamann A, Hu E, Spiegelman B, Flier JS, Moller DE (1996) Regulation of PPAR gamma gene expression by nutrition and obesity in rodents. J Clin Invest 97:2553–2561
Vidal-Puig AJ, Considine RV, Jimenez-Linan M, Werman A, Pories WJ, Caro JF, Flier JS (1997) Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids. J Clin Invest 99:2416–2422
Villarroya F, Giralt M, Iglesias R (1999) Retinoids and adipose tissues: metabolism, cell differentiation and gene expression. Int J Obes Relat Metab Disord 23:1–6
Xue JC, Schwarz EJ, Chawla A, Lazar MA (1996) Distinct stages in adipogenesis revealed by retinoid inhibition of differentiation after induction of PPARgamma. Mol Cell Biol 16:1567–1575
Yamauchi T, Waki H, Kamon J, Murakami K, Motojima K, Komeda K, Miki H, Kubota N, Terauchi Y, Tsuchida A, Tsuboyama-Kasaoka N, Yamauchi N, Ide T, Hori W, Kato S, Fukayama M, Akanuma Y, Ezaki O, Itai A, Nagai R, Kimura S, Tobe K, Kagechika H, Shudo K, Kadowaki T (2001) Inhibition of RXR and PPARgamma ameliorates diet-induced obesity and type 2 diabetes. J Clin Invest 108:1001–1013
Acknowledgments
This study was supported by grants of Conseil Régional d’Aquitaine. The authors wish to thank Kathryn Mayo for the English revision.
Author information
Authors and Affiliations
Corresponding author
Additional information
C. Bairras and A. Redonnet contributed equally to the work.
Rights and permissions
About this article
Cite this article
Bairras, C., Redonnet, A., Dabadie, H. et al. RARγ and TRβ expressions are decreased in PBMC and SWAT of obese subjects in weight gain. J Physiol Biochem 66, 29–37 (2010). https://doi.org/10.1007/s13105-010-0006-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13105-010-0006-x


