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 Dennis Jensen, Harold Robert (Bob) III Bergen, James L Kirkland

Research output: Contribution to journalArticle

18 Citations (Scopus)

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

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White Adipose Tissue
Macrophages
Chemokines
Inflammation
Monocytes
Interleukin-6
Intra-Abdominal Fat
Subcutaneous Fat
Tissue Expansion
Janus Kinases
Proteins
Chemotaxis
Neutralizing Antibodies
Proteomics
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

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

Cite this

Zhu, Y., Tchkonia, T., Stout, M. B., Giorgadze, N., Wang, L., Li, P. W., ... 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

Inflammation and the depot-specific secretome of human preadipocytes. / Zhu, Yi; Tchkonia, Tamara; Stout, Michael B.; Giorgadze, Nino; Wang, Libing; Li, Peter W.; Heppelmann, Carrie J.; Bouloumié, Anne; Jensen, Michael Dennis; Bergen, Harold Robert (Bob) III; Kirkland, James L.

In: Obesity, Vol. 23, No. 5, 01.05.2015, p. 989-999.

Research output: Contribution to journalArticle

Zhu, Y, Tchkonia, T, Stout, MB, Giorgadze, N, Wang, L, Li, PW, Heppelmann, CJ, Bouloumié, A, Jensen, MD, Bergen, HRBIII & Kirkland, JL 2015, 'Inflammation and the depot-specific secretome of human preadipocytes', Obesity, vol. 23, no. 5, pp. 989-999. https://doi.org/10.1002/oby.21053
Zhu Y, Tchkonia T, Stout MB, Giorgadze N, Wang L, Li PW et al. Inflammation and the depot-specific secretome of human preadipocytes. Obesity. 2015 May 1;23(5):989-999. https://doi.org/10.1002/oby.21053
Zhu, Yi ; Tchkonia, Tamara ; Stout, Michael B. ; Giorgadze, Nino ; Wang, Libing ; Li, Peter W. ; Heppelmann, Carrie J. ; Bouloumié, Anne ; Jensen, Michael Dennis ; Bergen, Harold Robert (Bob) III ; Kirkland, James L. / Inflammation and the depot-specific secretome of human preadipocytes. In: Obesity. 2015 ; Vol. 23, No. 5. pp. 989-999.
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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.",
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AU - Stout, Michael B.

AU - Giorgadze, Nino

AU - Wang, Libing

AU - Li, Peter W.

AU - Heppelmann, Carrie J.

AU - Bouloumié, Anne

AU - Jensen, Michael Dennis

AU - Bergen, Harold Robert (Bob) III

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N2 - 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.

AB - 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.

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