Type 2 diabetes-related proteins derived from an in vitro model of inflamed fat tissue

Jean Paul ten Klooster*, Alexandros Sotiriou, Sjef Boeren, Stefan Vaessen, Jacques Vervoort, Raymond Pieters

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

Currently, there is a worldwide increase of patients with type 2 diabetes (T2D). During the progression of healthy obese to T2D status, there is an influx of immune cells, in particular macrophages, into visceral adipose tissue, accompanied by an increase of inflammatory cytokines, such as, IL6, TNFα and Hp. To get a better insight in the underlying mechanisms, we performed a quantitative LCMS analysis on a modified in vitro assay, combining 3T3L1 adipocytes and activated RAW264.7 macrophages, thus mimicking inflamed adipose tissue. Clinically known proteins, e.g. IL6, TNFα AdipoQ, complement factor C3, B and D were identified, thus confirming the assay. In addition, we found 54 new proteins that can potentially be used for research into the mechanism of T2D. Comparison of our results to a study on human visceral fat of obese non-diabetic and obese diabetic subjects, indicated that AUH, NAGK, pCYT2, NNMT, STK39 and CSNK2A2 might indeed be linked to insulin resistance in humans. Moreover, the expression of some of these genes was also altered in human blood samples at early or later stages of insulin desensitization. Overall, we conclude that the direct contact co-culture of 3T3L1 adipocytes with activated macrophages could be a mechanistically relevant and partially translational model of inflamed visceral adipose tissue.
Original languageEnglish
Pages (from-to)81-92
JournalArchives of Biochemistry and Biophysics
Volume644
DOIs
Publication statusPublished - 15 Apr 2018

Fingerprint

Intra-Abdominal Fat
Macrophages
Medical problems
Type 2 Diabetes Mellitus
Fats
Tissue
Adipocytes
Interleukin-6
Assays
Insulin
Complement Factor D
Complement C3
Proteins
Complement Factor B
Coculture Techniques
Cell culture
Insulin Resistance
Adipose Tissue
Blood
Genes

Keywords

  • Adipocyte
  • AdipoQ
  • AUH
  • CSNK2A2
  • Haptoglobin
  • IL6
  • LPS
  • Macrophage
  • NAGK
  • NNMT
  • pCYT2
  • STK39
  • TNFα

Cite this

ten Klooster, Jean Paul ; Sotiriou, Alexandros ; Boeren, Sjef ; Vaessen, Stefan ; Vervoort, Jacques ; Pieters, Raymond. / Type 2 diabetes-related proteins derived from an in vitro model of inflamed fat tissue. In: Archives of Biochemistry and Biophysics. 2018 ; Vol. 644. pp. 81-92.
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Type 2 diabetes-related proteins derived from an in vitro model of inflamed fat tissue. / ten Klooster, Jean Paul; Sotiriou, Alexandros; Boeren, Sjef; Vaessen, Stefan; Vervoort, Jacques; Pieters, Raymond.

In: Archives of Biochemistry and Biophysics, Vol. 644, 15.04.2018, p. 81-92.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Type 2 diabetes-related proteins derived from an in vitro model of inflamed fat tissue

AU - ten Klooster, Jean Paul

AU - Sotiriou, Alexandros

AU - Boeren, Sjef

AU - Vaessen, Stefan

AU - Vervoort, Jacques

AU - Pieters, Raymond

PY - 2018/4/15

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N2 - Currently, there is a worldwide increase of patients with type 2 diabetes (T2D). During the progression of healthy obese to T2D status, there is an influx of immune cells, in particular macrophages, into visceral adipose tissue, accompanied by an increase of inflammatory cytokines, such as, IL6, TNFα and Hp. To get a better insight in the underlying mechanisms, we performed a quantitative LCMS analysis on a modified in vitro assay, combining 3T3L1 adipocytes and activated RAW264.7 macrophages, thus mimicking inflamed adipose tissue. Clinically known proteins, e.g. IL6, TNFα AdipoQ, complement factor C3, B and D were identified, thus confirming the assay. In addition, we found 54 new proteins that can potentially be used for research into the mechanism of T2D. Comparison of our results to a study on human visceral fat of obese non-diabetic and obese diabetic subjects, indicated that AUH, NAGK, pCYT2, NNMT, STK39 and CSNK2A2 might indeed be linked to insulin resistance in humans. Moreover, the expression of some of these genes was also altered in human blood samples at early or later stages of insulin desensitization. Overall, we conclude that the direct contact co-culture of 3T3L1 adipocytes with activated macrophages could be a mechanistically relevant and partially translational model of inflamed visceral adipose tissue.

AB - Currently, there is a worldwide increase of patients with type 2 diabetes (T2D). During the progression of healthy obese to T2D status, there is an influx of immune cells, in particular macrophages, into visceral adipose tissue, accompanied by an increase of inflammatory cytokines, such as, IL6, TNFα and Hp. To get a better insight in the underlying mechanisms, we performed a quantitative LCMS analysis on a modified in vitro assay, combining 3T3L1 adipocytes and activated RAW264.7 macrophages, thus mimicking inflamed adipose tissue. Clinically known proteins, e.g. IL6, TNFα AdipoQ, complement factor C3, B and D were identified, thus confirming the assay. In addition, we found 54 new proteins that can potentially be used for research into the mechanism of T2D. Comparison of our results to a study on human visceral fat of obese non-diabetic and obese diabetic subjects, indicated that AUH, NAGK, pCYT2, NNMT, STK39 and CSNK2A2 might indeed be linked to insulin resistance in humans. Moreover, the expression of some of these genes was also altered in human blood samples at early or later stages of insulin desensitization. Overall, we conclude that the direct contact co-culture of 3T3L1 adipocytes with activated macrophages could be a mechanistically relevant and partially translational model of inflamed visceral adipose tissue.

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