Decreased TLR3 in Hyperplastic Adipose Tissue, Blood and Inflamed Adipocytes is Related to Metabolic Inflammation
Background/Aims: Obesity is characterized by the immune activation that eventually dampens insulin sensitivity and changes metabolism. This study explores the impact of different inflammatory/ anti-inflammatory paradigms on the expression of toll-like receptors (TLR) found in adipocyte cultures, adi...
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Cell Physiol Biochem Press GmbH & Co KG
2018-11-01
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doaj-2ca5ca824dce4d28a45d9c22184365862020-11-24T21:40:12ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-11-015131051106810.1159/000495487495487Decreased TLR3 in Hyperplastic Adipose Tissue, Blood and Inflamed Adipocytes is Related to Metabolic InflammationJèssica LatorreJosé M. Moreno-NavarreteMónica SabaterMaria BuxoJosé I. Rodriguez-HermosaJordi GironesJosé M. FortRamón VilallongaWifredo RicartRafael SimoJose-Manuel Fernandez-RealFrancisco J. OrtegaBackground/Aims: Obesity is characterized by the immune activation that eventually dampens insulin sensitivity and changes metabolism. This study explores the impact of different inflammatory/ anti-inflammatory paradigms on the expression of toll-like receptors (TLR) found in adipocyte cultures, adipose tissue, and blood. Methods: We evaluated by real time PCR the impact of acute surgery stress in vivo (adipose tissue) and macrophages (MCM) in vitro (adipocytes). Weight loss was chosen as an anti-inflammatory model, so TLR were analyzed in fat samples collected before and after bariatric surgery-induced weight loss. Associations with inflammatory and metabolic parameters were analyzed in non-obese and obese subjects, in parallel with gene expression measures taken in blood and isolated adipocytes/ stromal-vascular cells (SVC). Treatments with an agonist of TLR3 were conducted in human adipocyte cultures under normal conditions and upon conditions that simulated the chronic low-grade inflammatory state of obesity. Results: Surgery stress raised TLR1 and TLR8 in subcutaneous (SAT), and TLR2 in SAT and visceral (VAT) adipose tissue, while decreasing VAT TLR3 and TLR4. MCM led to increased TLR2 and diminished TLR3, TLR4, and TLR5 expressions in human adipocytes. The anti-inflammatory impact of weight loss was concomitant with decreased TLR1, TLR3, and TLR8 in SAT. Cross-sectional associations confirmed increased V/ SAT TLR1 and TLR8, and decreased TLR3 in obese patients, as compared with non-obese subjects. As expected, TLR were predominant in SVC and adipocyte precursor cells, even though expression of all of them but TLR8 (very low levels) was also found in ex vivo isolated and in vitro differentiated adipocytes. Among SVC, CD14+ macrophages showed increased TLR1, TLR2, and TLR7, but decreased TLR3 mRNA. The opposite patterns shown for TLR2 and TLR3 in V/ SAT, SVC, and inflamed adipocytes were observed in blood as well, being TLR3 more likely linked to lymphocyte instead of neutrophil counts. On the other hand, decreased TLR3 in adipocytes challenged with MCM dampened lipogenesis and the inflammatory response to Poly(I:C). Conclusion: Functional variations in the expression of TLR found in blood and hypertrophied fat depots, namely decreased TLR3 in lymphocytes and inflamed adipocytes, are linked to metabolic inflammation.https://www.karger.com/Article/FullText/495487Toll-like receptorsGene expressionMacrophagesAdipocytesAdipose tissueBloodInnate immune systemObesityInflammationInsulin resistanceType 2 diabetesHumans |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jèssica Latorre José M. Moreno-Navarrete Mónica Sabater Maria Buxo José I. Rodriguez-Hermosa Jordi Girones José M. Fort Ramón Vilallonga Wifredo Ricart Rafael Simo Jose-Manuel Fernandez-Real Francisco J. Ortega |
spellingShingle |
Jèssica Latorre José M. Moreno-Navarrete Mónica Sabater Maria Buxo José I. Rodriguez-Hermosa Jordi Girones José M. Fort Ramón Vilallonga Wifredo Ricart Rafael Simo Jose-Manuel Fernandez-Real Francisco J. Ortega Decreased TLR3 in Hyperplastic Adipose Tissue, Blood and Inflamed Adipocytes is Related to Metabolic Inflammation Cellular Physiology and Biochemistry Toll-like receptors Gene expression Macrophages Adipocytes Adipose tissue Blood Innate immune system Obesity Inflammation Insulin resistance Type 2 diabetes Humans |
author_facet |
Jèssica Latorre José M. Moreno-Navarrete Mónica Sabater Maria Buxo José I. Rodriguez-Hermosa Jordi Girones José M. Fort Ramón Vilallonga Wifredo Ricart Rafael Simo Jose-Manuel Fernandez-Real Francisco J. Ortega |
author_sort |
Jèssica Latorre |
title |
Decreased TLR3 in Hyperplastic Adipose Tissue, Blood and Inflamed Adipocytes is Related to Metabolic Inflammation |
title_short |
Decreased TLR3 in Hyperplastic Adipose Tissue, Blood and Inflamed Adipocytes is Related to Metabolic Inflammation |
title_full |
Decreased TLR3 in Hyperplastic Adipose Tissue, Blood and Inflamed Adipocytes is Related to Metabolic Inflammation |
title_fullStr |
Decreased TLR3 in Hyperplastic Adipose Tissue, Blood and Inflamed Adipocytes is Related to Metabolic Inflammation |
title_full_unstemmed |
Decreased TLR3 in Hyperplastic Adipose Tissue, Blood and Inflamed Adipocytes is Related to Metabolic Inflammation |
title_sort |
decreased tlr3 in hyperplastic adipose tissue, blood and inflamed adipocytes is related to metabolic inflammation |
publisher |
Cell Physiol Biochem Press GmbH & Co KG |
series |
Cellular Physiology and Biochemistry |
issn |
1015-8987 1421-9778 |
publishDate |
2018-11-01 |
description |
Background/Aims: Obesity is characterized by the immune activation that eventually dampens insulin sensitivity and changes metabolism. This study explores the impact of different inflammatory/ anti-inflammatory paradigms on the expression of toll-like receptors (TLR) found in adipocyte cultures, adipose tissue, and blood. Methods: We evaluated by real time PCR the impact of acute surgery stress in vivo (adipose tissue) and macrophages (MCM) in vitro (adipocytes). Weight loss was chosen as an anti-inflammatory model, so TLR were analyzed in fat samples collected before and after bariatric surgery-induced weight loss. Associations with inflammatory and metabolic parameters were analyzed in non-obese and obese subjects, in parallel with gene expression measures taken in blood and isolated adipocytes/ stromal-vascular cells (SVC). Treatments with an agonist of TLR3 were conducted in human adipocyte cultures under normal conditions and upon conditions that simulated the chronic low-grade inflammatory state of obesity. Results: Surgery stress raised TLR1 and TLR8 in subcutaneous (SAT), and TLR2 in SAT and visceral (VAT) adipose tissue, while decreasing VAT TLR3 and TLR4. MCM led to increased TLR2 and diminished TLR3, TLR4, and TLR5 expressions in human adipocytes. The anti-inflammatory impact of weight loss was concomitant with decreased TLR1, TLR3, and TLR8 in SAT. Cross-sectional associations confirmed increased V/ SAT TLR1 and TLR8, and decreased TLR3 in obese patients, as compared with non-obese subjects. As expected, TLR were predominant in SVC and adipocyte precursor cells, even though expression of all of them but TLR8 (very low levels) was also found in ex vivo isolated and in vitro differentiated adipocytes. Among SVC, CD14+ macrophages showed increased TLR1, TLR2, and TLR7, but decreased TLR3 mRNA. The opposite patterns shown for TLR2 and TLR3 in V/ SAT, SVC, and inflamed adipocytes were observed in blood as well, being TLR3 more likely linked to lymphocyte instead of neutrophil counts. On the other hand, decreased TLR3 in adipocytes challenged with MCM dampened lipogenesis and the inflammatory response to Poly(I:C). Conclusion: Functional variations in the expression of TLR found in blood and hypertrophied fat depots, namely decreased TLR3 in lymphocytes and inflamed adipocytes, are linked to metabolic inflammation. |
topic |
Toll-like receptors Gene expression Macrophages Adipocytes Adipose tissue Blood Innate immune system Obesity Inflammation Insulin resistance Type 2 diabetes Humans |
url |
https://www.karger.com/Article/FullText/495487 |
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