Estrogen regulation of adiposity and fuel partitioning - Evidence of genomic and non-genomic regulation of lipogenic and oxidative pathways
Estrogen regulation of adiposity and fuel partitioning - Evidence of genomic and non-genomic regulation of lipogenic and oxidative pathways
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DOI：
10.1074/jbc.m507339200
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发表时间：
2005-10-28
影响因子：
4.8
通讯作者：
Greenberg, AS
中科院分区：
文献类型：
--
作者：
D'Eon, TM;Souza, SC;Greenberg, AS
更年期与肥胖增加和代谢疾病的风险增加有关。在卵巢切除（OVX）的绝经期啮齿动物模型中，通过雌激素（E2）替代预防肥胖增加，反映了E2的促肥胖作用和潜在的代谢作用。为了阐明E2调节脂肪储存和脂肪动员的代谢和分子机制，C57 BL/6小鼠卵巢切除，随机分配到雌激素（OVX-E2）或对照颗粒植入物（OVX-C），并配对喂养40天。E2治疗与脂肪量和脂肪细胞大小减少以及固醇调节元件结合蛋白1c控制下脂肪细胞中脂肪生成基因的下调相关。OVX-E2小鼠的脂肪细胞比配对对照（OVX）小鼠的脂肪细胞含有多3倍的周脂蛋白，并且这种差异与对儿茶酚胺的增强的离体脂解反应和禁食后更高水平的血清游离脂肪酸有关。在脂肪组织中，E2降低了肝脏和骨骼肌中脂肪生成基因的表达。在后者中，E2似乎通过上调过氧化物酶体增殖激活剂受体-δ及其下游靶点的表达，以及通过直接和快速激活AMP激活的蛋白激酶，促进游离脂肪酸向氧化方向的分配，并远离甘油三酯储存。因此，新的基因组和非基因组行动的E2促进精益OVX小鼠独立的能量摄入减少。
Menopause is associated with increased adiposity and greater risk of metabolic disease. In the ovariectomized (OVX) rodent model of menopause, increased adiposity is prevented by estrogen (E2) replacement, reflecting both anorexigenic and potentially metabolic actions of E2. To elucidate metabolic and molecular mechanisms by which E2 regulates fat storage and fat mobilization independently of reduced energy intake, C57 BL/6 mice were ovariectomized, randomized to estrogen (OVX-E2) or control pellet implants (OVX-C), and pairfed for 40 days. E2 treatment was associated with reduced adipose mass and adipocyte size and downregulation of lipogenic genes in adipocytes under the control of sterol-regulatory element-binding protein 1c. Adipocytes of OVX-E2 mice contained > 3-fold more perilipin protein than adipocytes of pairfed control ( OVX) mice, and this difference was associated with enhanced ex vivo lipolytic response to catecholamines and with greater levels of serum-free fatty acids following fasting. As in adipose tissue, E2 decreased the expression of lipogenic genes in liver and skeletal muscle. In the latter, E2 appears to promote the partitioning of free fatty acids toward oxidation and away from triglyceride storage by up-regulating the expression of peroxisome proliferation activator receptor-delta and its downstream targets and also by directly and rapidly activating AMP-activated protein kinase. Thus, novel genomic and non-genomic actions of E2 promote leanness in OVX mice independently of reduced energy intake.