Inflammation triggers specific microRNA profiles in human adipocytes and macrophages and in their supernatants.
BACKGROUND
The 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.


RESULTS
Differentiated 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).


CONCLUSIONS
Inflammation 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.
Department of Diabetes, Endocrinology and Nutrition (UDEN), Institut d'Investigació Biomédica de Girona (IdIBGi), Avinguda de França s/n, 17007 Girona, Spain ; CIBER de la Fisiopatología de la Obesidad y la Nutrición (CIBERobn, CB06/03) and Instituto de Salud Carlos III (ISCIII), Sinesio Delgado 4, 28029 Madrid, Spain.
Francisco José
FJ
Ortega
Department of Diabetes, Endocrinology and Nutrition (UDEN), Institut d'Investigació Biomédica de Girona (IdIBGi), Avinguda de França s/n, 17007 Girona, Spain.
María
M
Moreno
Joint BSC-CRG-IRB program on Computational Biology, Barcelona Supercomputing Center, Baldiri Reixac 10, 08028 Barcelona, Spain.
Josep María
JM
Mercader
Department of Diabetes, Endocrinology and Nutrition (UDEN), Institut d'Investigació Biomédica de Girona (IdIBGi), Avinguda de França s/n, 17007 Girona, Spain ; CIBER de la Fisiopatología de la Obesidad y la Nutrición (CIBERobn, CB06/03) and Instituto de Salud Carlos III (ISCIII), Sinesio Delgado 4, 28029 Madrid, Spain.
José María
JM
Moreno-Navarrete
Department of Diabetes, Endocrinology and Nutrition (UDEN), Institut d'Investigació Biomédica de Girona (IdIBGi), Avinguda de França s/n, 17007 Girona, Spain.
Núria
N
Fuentes-Batllevell
Department of Diabetes, Endocrinology and Nutrition (UDEN), Institut d'Investigació Biomédica de Girona (IdIBGi), Avinguda de França s/n, 17007 Girona, Spain.
Mònica
M
Sabater
Department of Diabetes, Endocrinology and Nutrition (UDEN), Institut d'Investigació Biomédica de Girona (IdIBGi), Avinguda de França s/n, 17007 Girona, Spain ; CIBER de la Fisiopatología de la Obesidad y la Nutrición (CIBERobn, CB06/03) and Instituto de Salud Carlos III (ISCIII), Sinesio Delgado 4, 28029 Madrid, Spain.
Wifredo
W
Ricart
Department of Diabetes, Endocrinology and Nutrition (UDEN), Institut d'Investigació Biomédica de Girona (IdIBGi), Avinguda de França s/n, 17007 Girona, Spain ; CIBER de la Fisiopatología de la Obesidad y la Nutrición (CIBERobn, CB06/03) and Instituto de Salud Carlos III (ISCIII), Sinesio Delgado 4, 28029 Madrid, Spain.
José Manuel
JM
Fernández-Real
Adipocytes; Adipose tissue; Inflammation; Macrophages; Obesity; Profiling; RT-PCR; microRNAs