Xu Feng, Li Fu-Xing-Zi, Lin Xiao, Zhong Jia-Yu, Wu Feng, Shan Su-Kang, Tan Chang-Ming, Yuan Ling-Qing, Liao Xiao-Bo
Department of Endocrinology and Metabolism, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, National Clinical Research Center for Metabolic Diseases, The Second Xiang-Ya Hospital, Central South University, Changsha 410011, Hunan, People's Republic of China.
Department of Geriatrics, The Second Xiang-Ya Hospital, Central South University, Changsha 410011, People's Republic of China.
Aging (Albany NY). 2019 Oct 25;11(20):8760-8776. doi: 10.18632/aging.102251.
Adipose tissue-derived adipokines mediate various kind of crosstalk between adipose tissue and other organs and thus regulate metabolism balance, inflammation state as well as disease progression. In particular, omentin-1, a newly found adipokine, has been reported to exhibit anti-calcification effects and . However, little is known about the function of endogenous adipose tissue-derived omentin-1 in arterial calcification and the detailed mechanism involved. Here, we demonstrated that global omentin-1 knockout (omentin-1) resulted in more obvious arterial calcification in 5/6-nephrectomy plus high phosphate diet treated (5/6 NTP) mice while overexpression of omentin-1 attenuated attenuates osteoblastic differentiation and mineralisation of VSMCs and 5/6 NTP-induced mice arterial calcification . Moreover, we found that omentin-1 induced AMPK and Akt activation while inhibition of AMP-activated protein kinase (AMPK) and Akt signaling reversed the anti-calcification effect induced by omentin-1 both and . Our results suggest that adipose tissue-derived omentin-1 serves as a potential therapeutic target for arterial calcification and cardiovascular disease.
脂肪组织衍生的脂肪因子介导脂肪组织与其他器官之间的各种相互作用,从而调节代谢平衡、炎症状态以及疾病进展。特别是,网膜素-1作为一种新发现的脂肪因子,已被报道具有抗钙化作用。然而,关于内源性脂肪组织衍生的网膜素-1在动脉钙化中的功能及其具体机制知之甚少。在此,我们证明,在5/6肾切除加高脂饮食处理(5/6 NTP)的小鼠中,全身性网膜素-1基因敲除(omentin-1)导致更明显的动脉钙化,而网膜素-1的过表达减弱了血管平滑肌细胞的成骨分化和矿化以及5/6 NTP诱导的小鼠动脉钙化。此外,我们发现网膜素-1诱导AMPK和Akt激活,而抑制AMP激活的蛋白激酶(AMPK)和Akt信号传导则逆转了网膜素-1诱导的抗钙化作用。我们的结果表明,脂肪组织衍生的网膜素-1是动脉钙化和心血管疾病的潜在治疗靶点。