Sousa-Pinto Bernardo, Gonçalves Laura, Rodrigues Adriana R, Tomada Inês, Almeida Henrique, Neves Delminda, Gouveia Alexandra M
Department of Experimental Biology, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-450, Porto, Portugal; Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-450, Porto, Portugal; Laboratory of Immunology, Basic and Clinical Immunology Unit, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319, Porto, Portugal.
Department of Experimental Biology, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-450, Porto, Portugal.
J Nutr Biochem. 2016 Dec;38:107-115. doi: 10.1016/j.jnutbio.2016.07.017. Epub 2016 Aug 26.
Transforming growth factor beta (TGF-β) plays an important role in the pathogenesis of obesity, influencing the release of inflammation mediators and promoting remodeling and collagen deposition in the adipose tissue (AT). In this context, this work aims to elucidate whether TGF-β and Smad-dependent or Smad-independent signaling pathways contribute to regional differentiation of AT in high-fat diet (HFD) and energy-restricted (ER) rat models. For this, TGF-β, TGF-β receptors I and II, PAI-1 and GLUT4 mRNA levels were quantified by real-time PCR, and western blotting assays allowed the semiquantification of TGF-β and proteins from Smad3, ERK1/2 and Akt signaling pathways in subcutaneous and visceral (epididymal, retroperitoneal and mesenteric) fat depots from control, HFD and ER-treated rats. HFD was associated to increased levels of TGF-β and PAI-1 mRNA in epididymal and retroperitoneal visceral fat depots, while ER diet induced a reduction of TGF-β mRNA levels in mesenteric, but surprisingly an increase in retroperitoneal fat. Regarding the different signaling pathways, contrarily to what was found for Smad3, activation of ERK1/2 and Akt in response to HFD was detected in all the visceral but not in subcutaneous fat depots. ER-treated rats presented a more heterogeneous signaling response, as well as decreased TGF-β receptors expression, in the different visceral fat depots. In conclusion, subcutaneous and visceral AT respond differently to distinct diet patterns regarding TGF-β expression and activated signaling pathways. Furthermore, the present study points that visceral AT should not be understood as a homogeneous entity since that response also varied in the different fat depots.
转化生长因子β（TGF-β）在肥胖发病机制中起重要作用，影响炎症介质的释放，并促进脂肪组织（AT）的重塑和胶原蛋白沉积。在此背景下，本研究旨在阐明TGF-β以及Smad依赖或非Smad依赖的信号通路是否促成高脂饮食（HFD）和能量限制（ER）大鼠模型中AT的区域分化。为此，通过实时PCR定量检测TGF-β、TGF-β受体I和II、PAI-1和GLUT4的mRNA水平，蛋白质免疫印迹分析对来自对照、HFD和ER处理大鼠的皮下和内脏（附睾、腹膜后和肠系膜）脂肪库中TGF-β以及Smad3、ERK1/2和Akt信号通路的蛋白质进行半定量分析。HFD与附睾和腹膜后内脏脂肪库中TGF-β和PAI-1 mRNA水平升高有关，而ER饮食导致肠系膜中TGF-β mRNA水平降低，但令人惊讶的是腹膜后脂肪中TGF-β mRNA水平升高。关于不同的信号通路，与Smad3的情况相反，在所有内脏脂肪库中均检测到HFD诱导的ERK1/2和Akt激活，但皮下脂肪库未检测到。ER处理的大鼠在不同的内脏脂肪库中呈现出更异质的信号反应，以及TGF-β受体表达降低。总之，皮下和内脏AT在TGF-β表达和激活的信号通路上对不同饮食模式的反应不同。此外，本研究指出，内脏AT不应被视为一个同质实体，因为不同脂肪库中的反应也有所不同。
