Estrogen supplementation deteriorates visceral adipose function in aged postmenopausal subjects via Gas5 targeting IGF2BP1
Estrogen supplementation deteriorates visceral adipose function in aged postmenopausal subjects via Gas5 targeting IGF2BP1
复制标题
雌激素补充剂通过靶向 IGF2BP1 的 Gas5 恶化绝经后老年受试者的内脏脂肪功能
DOI：
10.1016/j.exger.2022.111796
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发表时间：
2022-04-06
影响因子：
3.9
通讯作者：
Yu, Jing
中科院分区：
文献类型：
--
作者：
Lv, Yifan;Wang, Fengliang;Yu, Jing
内脏脂肪增加与一系列代谢并发症密切相关。绝经后妇女内脏脂肪积累、代谢紊乱和心血管事件发生率高的风险增加。然而，雌激素替代疗法对不同年龄绝经后妇女内脏脂肪组织的影响仍存在争议，其潜在机制尚不清楚。因此，了解雌激素替代疗法何时影响内脏脂肪组织（VAT）的功能是很重要的。因此，我们收集了绝经前和绝经后女性的VAT，我们观察到绝经后女性VAT中促炎因子和胰岛素抵抗诱导因子增加，胰岛素敏感因子和产热因子减少。从不同年龄的女性VAT中分离的脂肪细胞分析表明，绝经后女性雌激素治疗后，脂联素和褐变特征基因显著降低，但在年轻组中没有改变。在老年雌性小鼠（22 m）中补充雌激素可显著防止内脏脂肪堆积。然而，它通过诱导促炎因子和胰岛素抵抗诱导因子，降低胰岛素致敏因子和产热因子，使VAT功能恶化。机制上，雌激素通过结合ERa诱导绝经前妇女长链非编码RNA Gas5的表达，从而抑制IGF2BP1维持VAT功能。绝经后，随着VAT中ERa/ERp比值的逆转，补充雌激素主要通过ERp起作用，导致Gas5表达水平降低，最终导致VAT功能障碍。我们的研究证实了补充雌激素对老年绝经后人群VAT功能的不良影响，并进一步阐明了相关机制。
Increased visceral fat is strongly associated with a series of metabolic complications. Postmenopausal women have an increased risk of visceral fat accumulation, metabolic disorders, and a high incidence of cardiovascular events. However, the effect of estrogen replacement therapy on visceral adipose tissue among postmenopausal women of different ages remains controversial, and the underlying mechanism remains unclear. Hence, it is important to understand when estrogen replacement therapy affects the function of visceral adipose tissue (VAT). Therefore, we collected VAT from pre- and post-menopausal females and we observed increased proinflammatory cytokines and insulin resistance-inducing factors, decreased insulin-sensitizing factors, and thermogenic factors in VAT of postmenopausal women. The analysis of adipocytes isolated from the VAT of females of different ages indicated that adiponectin and browning signature genes were significantly decreased with estrogen treatment in postmenopausal women, but were not altered in the young group. Estrogen supplementation in aged female mice (22 m) significantly prevented visceral fat accumulation. However, it deteriorated VAT function by inducing pro-inflammatory cytokines and insulin resistance-inducing factors and decreasing insulin-sensitizing and thermogenic factors. Mechanistically, estrogen induced the expression of long non-coding RNA Gas5 via binding ERa in premenopausal women, which therefore suppressed IGF2BP1 to maintain VAT function. After menopause, with the reversal of ERa/ERp ratio in VAT, estrogen supplementation mainly worked through ERp, which led to low expression levels of Gas5 and eventually caused VAT dysfunction. Our study demonstrated the adverse effects of estrogen supplementation on VAT function in aged postmenopausal population and further elucidated the involved mechanism.