Research Paper Volume 11, Issue 20 pp 8760—8776
Adipose tissue-derived omentin-1 attenuates arterial calcification via AMPK/Akt signaling pathway
- 1 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
- 2 Department of Geriatrics, The Second Xiang-Ya Hospital, Central South University, Changsha 410011, People’s Republic of China
- 3 Department of Pathology, The Second Xiang-Ya Hospital, Central South University, Changsha 410011, People’s Republic of China
- 4 Department of Cardiovascular Surgery, The Second Xiang-Ya Hospital, Central South University, Changsha 410011, People’s Republic of China
received: May 26, 2019 ; accepted: September 2, 2019 ; published: October 25, 2019 ;https://doi.org/10.18632/aging.102251
How to Cite
Copyright © 2019 Xu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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 in vitro and in vivo. 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 in vitro and 5/6 NTP-induced mice arterial calcification in vivo. 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 in vitro and in vivo. Our results suggest that adipose tissue-derived omentin-1 serves as a potential therapeutic target for arterial calcification and cardiovascular disease.
ACC: acetyl-CoA carboxylase; Ad-Gal: adenovirus-encoding β-galactosidase; Ad-Ome: adenovirus-encoding omentin-1; ALP: alkaline phosphatase; AMPK: AMP-activated protein kinase; β-GP: beta-glycerophosphate; CVSMCs: calcifying vascular smooth muscle cells; NTP: nephrectomy mice with high-phosphate diet; OC: osteocalcin; Omentin-1-/- mice: omentin-1 knockout mice; PBS: phosphate-buffered saline; p-ACCα: phosphorylate acetyl-CoA carboxylase; p-AMPK: phosphorylate AMP-activated protein kinase; RANKL: receptor activator of nuclear factor-κB ligand; Runx2: runt related transcription factor 2; SD: standard deviation; VSMCs: vascular smooth muscle cells; WT: wild-type.