Abstract

BackgroundThe relevance of microRNAs (miRNAs) in adipose tissue is increasingly recognized, being intrinsically linked to different pathways, including obesity-related inflammation. In this study, we aimed to characterize the changes induced by inflammation on the miRNA pattern of human adipocytes and macrophages. Therefore, an extensive profile of 754 common miRNAs was assessed in cells (human primary mature adipocytes, and the macrophage-like cell line THP-1) and in their supernatants (SN) using TaqMan low-density arrays. These profiles were evaluated at the baseline and after administration of lipopolysaccharide (LPS, 10 ng/ml) and LPS-conditioned medium from M1 macrophages (MCM, 5%). The miRNAs that experienced the most dramatic changes were studied in subcutaneous human adipose tissue before and approximately 2 years after bariatric surgery-induced weight loss.ResultsDifferentiated adipocytes expressed 169 miRNAs, being 85 detectable in the SN. In M1 macrophages, 183 miRNAs were detected, being 106 also present in the SN. Inflammation led to an increased number of miRNAs detectable in cells and in their SNs in both adipocytes (+8.3% and +24.7%) and M1 macrophages (+1.4% and +5%, respectively). Indeed, under inflammatory conditions, adipocytes and M1 macrophages shared the expression of 147 (+9%) miRNAs, and 100 (+41%) common miRNAs were found in their SNs. Twelve of these factors were also linked to inflammation in whole adipose tissue from obese subjects. Interestingly, miR-221 (2-fold, P = 0.002), miR-222 (2.5-fold, P = 0.04), and miR-155 (5-fold, P = 0.015) were increased in inflamed adipocytes and in their SNs (15-, 6-, and 4-fold, respectively, all P < 0.001). Furthermore, their expressions in human adipose tissue concordantly decreased after weight loss (−51%, P = 0.003, −49%, P = 0.03, and −54.4%, P = 0.005, respectively).ConclusionsInflammation induces a specific miRNA pattern in adipocytes and M1 macrophages, with impact on the physiopathology of obesity-induced inflammation of adipose tissue. The crosstalk between cells should be investigated further.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-015-0083-3) contains supplementary material, which is available to authorized users.

Highlights

  • The relevance of microRNAs in adipose tissue is increasingly recognized, being intrinsically linked to different pathways, including obesity-related inflammation

  • We aimed to evaluate the main effects of inflammation on the miRNA profile of differentiated human adipocytes, the macrophage-like cell line THP-1 (M1), and in their supernatants (SNs)

  • The inflammatory reaction of LPSstimulated M1 macrophages, as inferred from changes in the expression of well-recognized pro-inflammatory genes such as IL-6 and TNFα (17.7-fold change, P = 0.002, and 4.9-fold change, P = 0.001, respectively), did not show such great impact, when compared to the changes accounted in mature adipocytes upon inflammation (Table 1)

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Summary

Introduction

The relevance of microRNAs (miRNAs) in adipose tissue is increasingly recognized, being intrinsically linked to different pathways, including obesity-related inflammation. An extensive profile of 754 common miRNAs was assessed in cells (human primary mature adipocytes, and the macrophage-like cell line THP-1) and in their supernatants (SN) using TaqMan low-density arrays. These profiles were evaluated at the baseline and after administration of lipopolysaccharide (LPS, 10 ng/ml) and LPS-conditioned medium from M1 macrophages (MCM, 5%). Weight loss is known to result in reduced macrophage infiltration in parallel to decreased expression of proinflammatory genes [7,8] Many of these factors are able to maintain sustained subclinical inflammation in obese AT, and activate other immune cells [9,10].

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