Circulating profiling reveals the effect of a polyunsaturated fatty acid-enriched diet on common microRNAs.

BACKGROUND: Consumption of long-chain polyunsaturated fatty acids (PUFAs), which are abundant in seafood and nuts, ameliorates components of the metabolic syndrome. Circulating microRNAs (miRNAs) have demonstrated to be valuable biomarkers of metabolic diseases. Here, we investigated whether a sustained nuts-enriched diet can lead to changes in circulating miRNAs, in parallel to the dietary modification of fatty acids (FAs). METHODS AND RESULTS: The profile of 192 common miRNAs was assessed (TaqMan low-density arrays) in plasma from 10 healthy women before and after an 8-week trial with a normocaloric diet enriched with PUFAs (30 g/day of almonds and walnuts). The most relevant miRNAs were validated in an extended sample of 30 participants (8 men and 22 women). Adiponectin was measured by immunoassay and FAs by gas liquid chromatography coupled to mass spectrometry. The percentage of both ω-3 (P=.01) and ω-6 (P=.029) PUFAs of dietary origin (as inferred from plasma FA concentrations) increased, whereas saturated FAs decreased (P=.0008). Concomitantly with changes in circulating FAs, several miRNAs were modified by treatment, including decreased miR-328, miR-330-3p, miR-221 and miR-125a-5p, and increased miR-192, miR-486-5p, miR-19b, miR-106a, miR-769-5p, miR-130b and miR-18a. Interestingly, miR-106a variations in plasma correlated with changes in PUFAs, while miR-130b (r=0.58, P=.003) and miR-221 (r=0.46, P=.03) reflected changes in C-reactive protein. The dietary modulation of miR-125a-5p mirrored changes in fasting triglycerides (r=-0.44, P=.019) and increased adiponectin (r=0.43, P=.026). CONCLUSION: Dietary FAs (as inferred from plasma FA concentration) are linked to changes in circulating miRNAs, which may be modified by a PUFAs-enriched diet.

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.