Departamento de Fisiologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, Brazil.
Am J Physiol Endocrinol Metab. 2020 Aug 1;319(2):E427-E437. doi: 10.1152/ajpendo.00094.2020. Epub 2020 Jul 14.
Menopause is often accompanied by visceral obesity. With the aim of exploring the consequences of ovarian failure on visceral fat, we evaluated the effects of ovariectomy and estrogen replacement on the proteome/phosphoproteome and on the fatty acid profile of the retroperitoneal adipose depot (RAT) of rats. Eighteen 3-mo-old female Wistar rats were either ovariectomized or sham operated and fed with standard chow for 3 mo. A subgroup of ovariectomized rats received estradiol replacement. RAT samples were analyzed with data-independent acquisitions LC-MS/MS, and pathway analysis was performed with the differentially expressed/phosphorylated proteins. RAT lipid profile was analyzed by gas chromatography. Ovariectomy induced high adiposity and insulin resistance and promoted alterations in protein expression and phosphorylation. Pathway analysis showed that five pathways were significantly affected by ovariectomy, namely, metabolism of lipids (including fatty acid metabolism and mitochondrial fatty acid β-oxidation), fatty acyl-CoA biosynthesis, innate immune system (including neutrophil degranulation), metabolism of vitamins and cofactors, and integration of energy metabolism (including ChREBP activates metabolic gene expression). Lipid profile analysis showed increased palmitic and palmitoleic acid content. The analysis of the data indicated that ovariectomy favored lipogenesis whereas it impaired fatty acid oxidation and induced a proinflammatory state in the visceral adipose tissue. These effects are consistent with the findings of high adiposity, hyperleptinemia, and impaired insulin sensitivity. The observed alterations were partially attenuated by estradiol replacement. The data point to a role of disrupted lipid metabolism in adipose tissue in the genesis of obesity after menopause.
绝经通常伴随着内脏肥胖。为了探索卵巢衰竭对内脏脂肪的影响，我们评估了卵巢切除术和雌激素替代对大鼠腹膜后脂肪组织（RAT）的蛋白质组/磷酸蛋白质组以及脂肪酸谱的影响。18 只 3 月龄雌性 Wistar 大鼠接受卵巢切除术或假手术，并接受标准饲料喂养 3 个月。一部分卵巢切除大鼠接受雌二醇替代治疗。使用非依赖性采集 LC-MS/MS 分析 RAT 样本，并使用差异表达/磷酸化蛋白进行途径分析。通过气相色谱法分析 RAT 脂质谱。卵巢切除术导致肥胖和胰岛素抵抗，并促进蛋白质表达和磷酸化的改变。途径分析显示，有 5 条途径受到卵巢切除术的显著影响，即脂质代谢（包括脂肪酸代谢和线粒体脂肪酸β氧化）、脂肪酸酰基辅酶 A 生物合成、固有免疫系统（包括嗜中性粒细胞脱颗粒）、维生素和辅因子代谢以及能量代谢整合（包括 ChREBP 激活代谢基因表达）。脂质谱分析显示棕榈酸和棕榈油酸含量增加。数据分析表明，卵巢切除术有利于脂肪生成，而损害脂肪酸氧化，并在内脏脂肪组织中诱导炎症状态。这些影响与高肥胖、高瘦素血症和胰岛素敏感性受损的发现一致。雌二醇替代治疗部分减轻了观察到的变化。数据表明，脂肪组织中脂质代谢紊乱在绝经后肥胖的发生中起作用。
