Tomicek Nanette J, Lancaster Timothy S, Korzick Donna H
Intercollege Program in Physiology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Gend Med. 2011 Oct;8(5):325-33. doi: 10.1016/j.genm.2011.05.010. Epub 2011 Jul 22.
Obesity and associated metabolic and cardiovascular disease risk are correlated with reduced circulating adiponectin (APN) levels. Metabolic and cardiovascular disease risk is also increased after menopause and may be linked to disturbances in estrogen receptor (ER) signaling in adipose.
We hypothesized that age-associated estrogen (E(2))-deficiency alters the ERα/β ratio in adipose tissue and increases risk for metabolic disease via APN-ac activated mechanisms.
Visceral adipose was isolated from adult (6 months) and aged (24 months) female Fisher 344 rats (n = 5-6/group) with ovaries intact or removed by surgical ovariectomy (OVX) and subjected to western blotting.
Notably, weight was greatest in aged OVX rats (P < 0.01) and associated with a 2-fold increase in ERβ protein versus adult intact rats (P < 0.001). ER levels were increased in aged OVX versus adult OVX rats. Intra-adipocyte APN was also increased in aged OVX rats versus all groups (P < 0.01), whereas circulating APN levels decreased in aged OVX versus adult OVX rats (P < 0.05). Endoplasmic reticulum protein of 44 kDa (Erp44) levels remained the same (P = 0.09). Adiponectin receptor-1 (AdipoR1) and peroxisome proliferator-activated receptor-α (PPAR-α) were also unchanged. AdipoR2, PPAR-γ, and phosphorylated adenosine monophosphate-dependant kinase (pAMPK) to total AMPK ratio all decreased with age (P < 0.05).
Collectively, these data suggested that age-associated increases in ERβ paired with decreased PPAR-γ levels might predispose E(2)-deficient postmenopausal women for increased adiposity and associated metabolic and cardiovascular disease risk. Reduced circulating APN and AdipoR2 levels might contribute to age and E(2)-deficiency linked disease progression.
肥胖以及相关的代谢和心血管疾病风险与循环脂联素（APN）水平降低相关。绝经后代谢和心血管疾病风险也会增加，这可能与脂肪组织中雌激素受体（ER）信号传导紊乱有关。
我们假设年龄相关的雌激素（E₂）缺乏会改变脂肪组织中ERα/β比例，并通过APN激活的机制增加代谢疾病风险。
从成年（6个月）和老年（24个月）雌性Fisher 344大鼠（每组n = 5 - 6）中分离内脏脂肪，这些大鼠卵巢完整或通过手术卵巢切除术（OVX）切除卵巢，然后进行蛋白质免疫印迹分析。
值得注意的是，老年OVX大鼠体重最大（P < 0.01），与成年完整大鼠相比，ERβ蛋白增加了2倍（P < 0.001）。与成年OVX大鼠相比，老年OVX大鼠的ER水平升高。与所有组相比，老年OVX大鼠脂肪细胞内APN也增加（P < 0.01），而与成年OVX大鼠相比，老年OVX大鼠循环APN水平降低（P < 0.05）。44 kDa的内质网蛋白（Erp44）水平保持不变（P = 0.09）。脂联素受体-1（AdipoR1）和过氧化物酶体增殖物激活受体-α（PPAR-α）也未改变。AdipoR2、PPAR-γ以及磷酸化的腺苷单磷酸依赖性激酶（pAMPK）与总AMPK的比例均随年龄降低（P < 0.05）。
总体而言，这些数据表明，年龄相关的ERβ增加与PPAR-γ水平降低可能使绝经后雌激素缺乏的女性更容易肥胖，并增加相关代谢和心血管疾病风险。循环APN和AdipoR2水平降低可能导致与年龄和雌激素缺乏相关的疾病进展。
