Inflammation and the depot-specific secretome of human preadipocytes

Yi Zhu, Tamara Tchkonia, Michael B. Stout, Nino Giorgadze, Libing Wang, Peter W. Li, Carrie J. Heppelmann, Anne Bouloumié, Michael D. Jensen, H. Robert Bergen, James L. Kirkland

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Objective Visceral white adipose tissue (WAT) expansion and macrophage accumulation are associated with metabolic dysfunction. Visceral WAT typically shows greater macrophage infiltration. Preadipocytes show varying proinflammatory expression profiles among WAT depots. The objective was to examine the secretomes and chemoattractive properties of preadipocytes from visceral and subcutaneous WAT. Methods A label-free quantitative proteomics approach was applied to study secretomes of subcutaneous and omental preadipocytes from obese subjects. Enzyme-linked immunosorbent assays and chemotaxis assays were used to confirm proinflammatory chemokine secretion between depots. Results Preadipocyte secretomes showed greater variation between depots than did intracellular protein expression. Chemokines were the most differentially secreted proteins. Omental preadipocytes induced chemoattraction of macrophages and monocytes. Neutralizing antibodies to the identified chemokines reduced macrophage/monocyte chemoattraction. Subcutaneous preadipocytes treated with interleukin-6 (IL-6) resembled omental preadipocytes in terms of chemokine secretion and macrophage/monocyte chemoattraction. Janus-activated kinase (JAK1/2) protein expression, which transduces IL-6 signaling, was higher in omental than subcutaneous preadipocytes and WAT. Inhibiting JAK in omental preadipocytes decreased chemokine secretion and macrophage/monocyte chemoattraction to levels closer to that observed in subcutaneous preadipocytes. Conclusions Secretomes of omental and subcutaneous preadipocytes are distinct, with the former inducing more macrophage/monocyte chemoattraction, in part through IL-6/JAK-mediated signaling.

Original languageEnglish (US)
Pages (from-to)989-999
Number of pages11
JournalObesity
Volume23
Issue number5
DOIs
StatePublished - May 1 2015

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

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    Zhu, Y., Tchkonia, T., Stout, M. B., Giorgadze, N., Wang, L., Li, P. W., Heppelmann, C. J., Bouloumié, A., Jensen, M. D., Robert Bergen, H., & Kirkland, J. L. (2015). Inflammation and the depot-specific secretome of human preadipocytes. Obesity, 23(5), 989-999. https://doi.org/10.1002/oby.21053