Unité de Nutrition et Neurosciences (U2N), Université Bordeaux 1, Avenue des Facultés, 33405 Talence, France.
J Physiol Biochem. 2010 Mar;66(1):29-37. doi: 10.1007/s13105-010-0006-x. Epub 2010 Apr 13.
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 RARgamma 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 TRbeta were observed in PBMC and SWAT of WG (-50.7% and -28%, respectively) just as for TRalpha in PBMC of WG (-19%). In contrast, retinoid X receptors alpha (RXRalpha) and RARalpha 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 RXRalpha was lower in SWAT of WG (-24.5%). As for PPARgamma, its mRNA level was significantly higher in PBMC of WG subjects (+34%) while its expression was not modified in SWAT, contrary to the PPARgamma2 isoform which was significantly higher. These data show that in both adipose tissue and blood compartment of obese subjects, expressions of RARgamma and TRbeta 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.
为了评估肥胖患者外周核受体的表达,我们测定并比较了外周血单个核细胞(PBMC)和皮下白色脂肪组织(SWAT)中不同视黄酸受体(RAR)、三碘甲状腺原氨酸(TR)和过氧化物酶体增殖物激活受体(PPAR)异构体的信使 RNA(mRNA)水平。研究了 12 名正常体重者和 68 名肥胖者,分为体重增加(WG)、体重稳定(WS)和体重减轻(WL)组。采用实时定量逆转录聚合酶链反应方法评估 PBMC 和 SWAT 中的核受体 mRNA 水平。肥胖患者的 PBMC 中 RARγ mRNA 水平明显低于 SWAT(WG-19%、WS-30%和 WL-24.7%),而 WG 的 SWAT 中 RARγ mRNA 水平降低了 50%。WG 的 PBMC 和 SWAT 中 TRβ mRNA 水平均降低(分别为-50.7%和-28%),而 WG 的 PBMC 中 TRα mRNA 水平降低了 19%。相反,视黄酸 X 受体α(RXRα)和 RARα mRNA 水平在肥胖患者的 PBMC 中升高(WG 分别升高 53%和 54.5%、WS 升高 56%和 67%、WL 升高 68%和 49.7%),而 WG 的 SWAT 中 RXRα表达降低了 24.5%。至于 PPARγ,其在 WG 患者的 PBMC 中的 mRNA 水平显著升高(34%),而在 SWAT 中则未改变,而 PPARγ2 异构体则显著升高。这些数据表明,在肥胖患者的脂肪组织和血液中,RARγ和 TRβ的表达均下调。因此,我们认为肥胖患者 PBMC 的表达可能构成核受体视黄酸和甲状腺状态的新的细胞指标。