Department of Emergency, Affiliated Xiaolan Hospital of Southern Medical University, Zhongshan, Guangdong, China.
Amino Acids. 2011 Nov;41(5):1223-31. doi: 10.1007/s00726-010-0800-3. Epub 2010 Nov 17.
Arterial calcification is positively associated with visceral adiposity, but the mechanisms remain unclear. Omentin is a novel adipokine that is selectively expressed in visceral adipose tissue. The levels of circulating omentin are decreased in obesity, and they correlate negatively with waist circumference. This study investigated the effects of omentin on the osteoblastic differentiation of calcifying vascular smooth muscle cells (CVSMCs), a subpopulation of aortic smooth muscle cells putatively involved in vascular calcification. Omentin inhibited mRNA expression of alkaline phosphatase (ALP) and osteocalcin; omentin also suppressed ALP activity, osteocalcin protein production, and the matrix mineralization. Furthermore, omentin selectively activated phosphatidylinositol 3-kinase (PI3K) downstream effector Akt. Moreover, inhibition of PI3K or Akt activation reversed the effects of omentin on ALP activity and the matrix mineralization. The present results demonstrate for the first time that omentin can inhibit osteoblastic differentiation of CVSMCs via PI3K/Akt signaling pathway, suggesting that the lower omentin levels in obese (specially visceral obese) subjects contribute to the development of arterial calcification, and omentin plays a protective role against arterial calcification.
动脉钙化与内脏肥胖呈正相关，但机制尚不清楚。网膜素是一种新型脂肪因子，选择性地在内脏脂肪组织中表达。肥胖患者循环网膜素水平降低，与腰围呈负相关。本研究探讨了网膜素对钙化血管平滑肌细胞（CVSMCs）成骨分化的影响，CVSMCs 是主动脉平滑肌细胞的一个亚群，可能与血管钙化有关。网膜素抑制碱性磷酸酶（ALP）和骨钙素的 mRNA 表达；网膜素还抑制 ALP 活性、骨钙素蛋白的产生和基质矿化。此外，网膜素选择性地激活了磷脂酰肌醇 3-激酶（PI3K）下游效应物 Akt。此外，抑制 PI3K 或 Akt 激活可逆转网膜素对 ALP 活性和基质矿化的作用。本研究结果首次证明，网膜素可通过 PI3K/Akt 信号通路抑制 CVSMCs 的成骨分化，提示肥胖（特别是内脏肥胖）患者网膜素水平降低可能导致动脉钙化的发生，而网膜素对动脉钙化起保护作用。
