Circulating microRNAs have a sex-specific association with metabolic syndrome

Abstract

BackgroundThe microRNAs let-7 g and miR-221 have been demonstrated to be related to the glucose metabolism. This study assessed the serum levels of these two microRNAs in subjects with and without metabolic syndrome (MetS).ResultsThe serum microRNA levels were detected in 102 subjects aged 40 to 80 years who were recruited from the general population. The status of MetS was defined by the Adult Treatment Panel III (ATP III) criteria modified for Asians. Subjects with histories of cardiovascular diseases or who were receiving treatment with hypoglycemic or lipid-lowering agents were excluded. The levels of both circulating microRNAs (let-7 g and miR-221) were higher in subjects with MetS (p = 0.004 and p = 0.01, respectively). The sex-specific analysis showed that the difference was more prominent in women (for both miRNAs, p < 0.05 in women and p > 0.1 in men). In the female subjects, increased expression of both microRNAs was associated with an increased number of MetS risk components (p = 0.002 for let-7 g and p = 0.022 for miR-221). Moreover, the elevation of serum let-7 g was significantly associated with a low level of high-density lipoprotein cholesterol (p = 0.022) and high blood pressure (p = 0.023). In contrast, the miR-221 level was not associated with any individual MetS risk component.ConclusionsThe circulating levels of let-7 g and miR-221 displayed a female-specific elevation in individuals with metabolic syndrome.

Blood-Based Biomarkers for Metabolic Syndrome

“…Targets IRS2 in liver cells and macrophages [19] miR-33a, miR-33b elevated in the serum of an Asian cohort with MetS (Table 2, row I) [37]. Levels of both miRNAs increased in parallel with increasing number of MetS components presented.…”

“…For individuals presenting with four to five components of MetS, let-7 g and miR-122 were both significantly increased. Moreover, the elevation of serum let-7 g was significantly associated with a low level of HDL-cholesterol and high blood pressure [37]. miR-122 has been shown to regulate FA metabolism, cholesterol synthesis, and cholesterol levels [38].…”

Early Origins of Health and Disease

“…It has been shown that miR-103, miR-107, and miR-33 regulated insulin sensitivity and glucose homeostasis [175À177]. Two circulating miRNAs (let-7 g and miR-221) have a female-specific elevation in individuals with MS [178]. Concerning the features of MS, blood miR-197, miR-23, and miR-509-5p positively correlated with BMI, and elevated circulating miR-130a and miR-195 were associated with high BP [179].…”

Intra-individual variation of miRNA expression levels in human plasma samples

“…miRNAs can be exported or released by cells and circulate with the blood in a remarkably stable form by packaging into microparticles, e.g., exosomes, microvesicles, or apoptotic bodies (4, 5), binding to RNA-binding proteins or high-density lipoprotein (6–8). Although the precise role of circulating miRNAs is still largely unknown, dysregulated expression of circulating miRNAs has been found to be associated with the occurrence of a variety of diseases including cancers (8, 9, 9–14), cardiovascular disease (15–20), diabetes mellitus (21), obesity (22, 23), neurodegenerative disease (24, 25), and autoimmune disease (26), as well as altered physiological states such as pregnancy (27). Thus, circulating miRNAs have become of increasing interest as non-invasive biomarkers for predicting disease risk and prognosis, as well as for cancer early diagnosis and monitoring of treatment responses.…”