Neovascular deterioration, impaired NADPH oxidase and inflammatory cytokine expression in adipose-derived multipotent cells from subjects with metabolic syndrome

Metabolism. 2017 Jun:71:132-143. doi: 10.1016/j.metabol.2017.03.012. Epub 2017 Mar 29.

Abstract

Objective: Expansion of adipose tissue depends on the growth of its vascular network and it has been shown that adipose tissue dysfunction in obese subjects with the metabolic syndrome is associated with decreased angiogenesis. However, some subjects with a high body mass index do not develop metabolic abnormalities associated with obesity. In this study we examined the neovascular properties, expression levels of proteins involved in cellular redox balance and inflammatory cytokines in adipose-derived multipotent mesenchymal cells (ASCs) of subjects with different metabolic profiles.

Materials/methods: We applied cell culture, flow cytometry, RT-qPCR and ELISA techniques to characterize the ASCs isolated from paired biopsies of visceral (visASCs) and subcutaneous (subASCs) adipose tissue from 39 subjects grouped into normal weight (Nw), obese without metabolic syndrome (NonMS) and with metabolic syndrome (MS).

Results: VisASCs and subASCs from MS subjects showed a decrease in tubules formation capacity compared to ASCs from NonMS subjects as well as changes in the expression levels of proteins involved in cell redox balance and secretion levels of proteins linked to the senescence-associated secretory phenotype. Deterioration in the neovascular properties of subASCs from the MS subjects was also evident in the decreased levels of VEGF secretion during adipogenesis and in the effects of the conditioned medium on endothelial cell tubule formation.

Conclusions: Our findings suggest a redox imbalance status in ASCs from subjects with metabolic syndrome and decreased their neovascular function that probably contributes to the vascular insufficiency of adipose depots.

Keywords: ASC; HGF; Metabolic syndrome; NOX; VEGF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism*
  • Adipogenesis / genetics
  • Adult
  • Blood Vessels / pathology*
  • Cell Survival
  • Cells, Cultured
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Endothelial Cells
  • Female
  • Gene Expression
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Male
  • Metabolic Syndrome / metabolism*
  • Metabolic Syndrome / pathology*
  • Microtubules
  • Multipotent Stem Cells / metabolism*
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism*
  • Neovascularization, Physiologic

Substances

  • Cytokines
  • NADPH Oxidases