TY - JOUR
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
N1 - Copyright © 2018 Elsevier Inc. All rights reserved.
PY - 2018/4/15
Y1 - 2018/4/15
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.
KW - Adipocyte
KW - TNFa
KW - Haptoglobin
KW - AdipoQ
KW - AUH
KW - NAGK
KW - pCYT2
KW - NNMT
KW - STK39
KW - CSNK2A2
KW - LPS
KW - Macrophage
U2 - 10.1016/j.abb.2018.03.003
DO - 10.1016/j.abb.2018.03.003
M3 - Article
C2 - 29526533
SN - 0003-9861
VL - 644
SP - 81
EP - 92
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
ER -