Adipose tissue-derived omentin-1 attenuates arterial calcification via AMPK/Akt signaling pathway

Aging (Albany NY). 2019 Oct 25;11(20):8760-8776. doi: 10.18632/aging.102251. Epub 2019 Oct 25.

Abstract

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.

Keywords: AMP-activated protein kinase; Akt; arterial calcification; omentin-1; smooth muscle differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Adipose Tissue / metabolism*
  • Animals
  • Calcinosis / chemically induced
  • Calcinosis / metabolism*
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism*
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism*
  • Humans
  • Lectins / genetics
  • Lectins / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Smooth, Vascular
  • Myocytes, Smooth Muscle
  • Osteocalcin / metabolism
  • Phosphorus, Dietary / adverse effects
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Random Allocation

Substances

  • Cytokines
  • GPI-Linked Proteins
  • Itln1 protein, mouse
  • Lectins
  • Phosphorus, Dietary
  • Osteocalcin
  • Protein Kinases
  • Proto-Oncogene Proteins c-akt
  • AMP-Activated Protein Kinase Kinases