Abstract：
Postmenopausal women experience bone loss and weight gain. To date, crosstalk between estrogen receptor signals and nuclear factor-κB (NF-κB) has been reported, and estrogen depletion enhances bone resorption by osteoclasts via NF-κB activation. However, it is unclear when and in which tissues NF-κB is activated after menopause, and how NF-κB acts as a common signaling molecule for postmenopausal weight gain and bone loss. Therefore, we examined the role of NF-κB in bone and energy metabolism following menopause. NF-κB reporter mice, which can be used to measure NF-κB activation in vivo, were ovariectomized (OVX) and the luminescence intensity after OVX increased in the metaphyses of the long bones and perigonadal white adipose tissue, but not in the other tissues. OVX was performed on wild-type (WT) and p65 mutant knock-in (S534A) mice, whose mutation enhances the transcriptional activity of NF-κB. Weight gain with worsening glucose tolerance was significant in S534A mice after OVX compared with those of WT mice. The bone density of the sham group in WT or S534A mice did not change, whereas in the S534A-OVX group it significantly decreased due to the suppression of bone formation and increase in bone marrow adipocytes. Disulfiram, an anti-alcoholic drug, suppressed OVX-induced activation of NF-κB in the metaphyses of long bones and white adipose tissue (WAT), as well as weight gain and bone loss. Overall, the activation of NF-κB in the metaphyses of long bones and WAT after OVX regulates post-OVX weight gain and bone loss.
摘要：
绝经后妇女经历骨质流失和体重增加。迄今为止,雌激素受体信号与核因子-κB(NF-κB)的串扰,雌激素消耗通过NF-κB激活增强破骨细胞的骨吸收。然而,目前尚不清楚何时以及在哪些组织中NF-κB在绝经后被激活，以及NF-κB如何作为绝经后体重增加和骨丢失的常见信号分子。因此,我们研究了NF-κB在绝经后骨骼和能量代谢中的作用。NF-κB报告小鼠,可用于测量体内NF-κB的激活，进行卵巢切除（OVX），OVX后的发光强度在长骨和周围白色脂肪组织的干is端增加，但不是在其他组织。在野生型（WT）和p65突变敲入（S534A）小鼠上进行OVX，其突变增强NF-κB的转录活性。与WT小鼠相比，OVX后S534A小鼠的体重增加和葡萄糖耐量恶化是显着的。假手术组WT或S534A小鼠的骨密度没有改变，而在S534A-OVX组中，由于骨形成的抑制和骨髓脂肪细胞的增加，它显着降低。双硫仑,一种抗酒精药物,抑制OVX诱导的NF-κB在长骨和白色脂肪组织（WAT）的干is端激活，以及体重增加和骨质流失。总的来说,OVX后长骨和WAT的干干yal端NF-κB的激活调节了OVX后的体重增加和骨丢失（241个字）。
