Ortega Francisco José, Moreno María, Mercader Josep María, Moreno-Navarrete José María, Fuentes-Batllevell Núria, Sabater Mònica, Ricart Wifredo, Fernández-Real José Manuel
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.
Department of Diabetes, Endocrinology and Nutrition (UDEN), Institut d'Investigació Biomédica de Girona (IdIBGi), Avinguda de França s/n, 17007 Girona, Spain.
Clin Epigenetics. 2015 Apr 24;7(1):49. doi: 10.1186/s13148-015-0083-3. eCollection 2015.
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.
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).
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.
微小RNA(miRNA)在脂肪组织中的相关性日益受到认可,其与包括肥胖相关炎症在内的不同途径存在内在联系。在本研究中,我们旨在描述炎症对人脂肪细胞和巨噬细胞miRNA模式的诱导变化。因此,使用TaqMan低密度芯片评估了细胞(人原代成熟脂肪细胞和巨噬细胞样细胞系THP-1)及其上清液(SN)中754种常见miRNA的广泛图谱。在基线以及给予脂多糖(LPS,10 ng/ml)和来自M1巨噬细胞的LPS条件培养基(MCM,5%)后对这些图谱进行评估。对经历最显著变化的miRNA在减重手术诱导体重减轻前和大约2年后的皮下人脂肪组织中进行了研究。
分化的脂肪细胞表达169种miRNA,其中85种可在SN中检测到。在M1巨噬细胞中,检测到183种miRNA,其中106种也存在于SN中。炎症导致脂肪细胞(分别增加8.3%和24.7%)和M1巨噬细胞(分别增加1.4%和5%)中细胞及其SN中可检测到的miRNA数量增加。实际上,在炎症条件下,脂肪细胞和M1巨噬细胞共有147种(增加9%)miRNA的表达,并且在它们的SN中发现了100种(增加41%)常见miRNA。其中12种因子也与肥胖受试者全脂肪组织中的炎症相关。有趣的是,miR-221(2倍,P = 0.002)、miR-222(2.5倍,P = 0.04)和miR-155(5倍,P = 0.015)在炎症脂肪细胞及其SN中增加(分别为15倍、6倍和4倍,所有P < 0.001)。此外,体重减轻后它们在人脂肪组织中的表达一致下降(分别为-51%,P = 0.003;-49%,P = 0.03;-54.4%,P = 0.005)。
炎症在脂肪细胞和M1巨噬细胞中诱导特定的miRNA模式,对肥胖诱导的脂肪组织炎症的病理生理学产生影响。细胞间的相互作用应进一步研究。