Amengual-Cladera Emilia, Capllonch-Amer Gabriela, Lladó Isabel, Gianotti Magdalena, Proenza Ana M
a Grup Metabolisme Energètic i Nutrició, Departament de Biologia Fonamental i Ciències de la Salut, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, Palma de Mallorca, Spain.
b Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y la Nutrición (CIBERobn, CB06/03/0043), Instituto de Salud Carlos III, C/Sinesio Delgado 4, 28029 Madrid, Spain.
Biochem Cell Biol. 2016 Apr;94(2):167-75. doi: 10.1139/bcb-2015-0077. Epub 2016 Feb 25.
Taking into account the sexual dimorphism previously found in white adipose tissue (WAT) regarding mitochondrial function and biogenesis, as well as insulin sensitivity, the aim of this study was to go further into the role of sex hormones in this dimorphism. To achieve this objective, we used ovariectomized rats and performed a screening by means of proteomic analyses of the periovarian WAT, combined with a study of the protein levels of specific factors involved in mitochondrial function. Rats were ovariectomized at 5 weeks of age and subcutaneously injected every 48 h with corn-oil (OVX group) or with 17β-estradiol (E2, 10 μg/kg body mass; OVX + E2 group) for 4 weeks prior to sacrifice. Beside proteomic analysis, protein levels of Transcription Factor A, Mitochondrial (TFAM), cytochrome oxidase (COX)II, and COXIV were determined by Western blot, and mRNA levels of peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, ERα, ERβ, lipoprotein lipase (LPL), peroxisome proliferator-activated receptor-γ (PPARγ), and adiponectin were quantified by real-time PCR. Our results show that ovariectomy leads to an increase in anabolic processes and inflammatory protein levels as well as to a decrease in some of the markers of mitochondrial function, which are restored, at least in part, by E2 supplementation. Indeed, this E2 supplementation seems to be counteracted by a decline in ERα and in the ERα to ERβ ratio values that could be directed to avoid an over-stimulation of the E2 signaling pathway, given the possibility of an activation of extra-gonadal steroid biosynthetic pathways.
考虑到先前在白色脂肪组织（WAT）中发现的关于线粒体功能和生物发生以及胰岛素敏感性的性别二态性，本研究的目的是进一步探究性激素在这种二态性中的作用。为实现这一目标，我们使用了去卵巢大鼠，并通过对卵巢周围WAT进行蛋白质组学分析进行筛选，同时研究参与线粒体功能的特定因子的蛋白质水平。大鼠在5周龄时进行去卵巢手术，并在处死前4周每48小时皮下注射玉米油（OVX组）或17β-雌二醇（E2，10μg/kg体重；OVX + E2组）。除蛋白质组学分析外，通过蛋白质印迹法测定线粒体转录因子A（TFAM）、细胞色素氧化酶（COX）II和COXIV的蛋白质水平，并通过实时PCR定量过氧化物酶体增殖物激活受体γ共激活因子（PGC）-1α、雌激素受体α（ERα）、雌激素受体β（ERβ）、脂蛋白脂肪酶（LPL）、过氧化物酶体增殖物激活受体γ（PPARγ）和脂联素的mRNA水平。我们的结果表明，去卵巢会导致合成代谢过程和炎症蛋白水平增加，以及一些线粒体功能标志物减少，而补充E2至少部分恢复了这些变化。事实上，这种E2补充似乎被ERα以及ERα与ERβ比值的下降所抵消，鉴于性腺外类固醇生物合成途径激活的可能性，这可能是为了避免E2信号通路的过度刺激。
