Circulating miR-143-3p inhibition protects against insulin resistance in Metabolic Syndrome via targeting of the insulin-like growth factor 2 receptor.

Metabolic syndrome (MetS) is characterized by a cluster of metabolic disorders including obesity, dyslipidemia, hyperglycemia, and hypertension. Here, we report that 27 microRNAs were found to be expressed differently in serum and urine samples of MetS patients compared to control subjects on microarray analysis. Further qualitative real time- polymerase chain reaction analyses confirmed that circulating levels of miR-143-3p were significantly elevated in MetS patients compared with controls, both in serum and urine samples. After accounting for confounding factors, high levels of miR-143-3p remained an independent risk factor for insulin resistance. Inhibition of miR-143-3p expression in mice protected against development of obesity-associated insulin resistance. Furthermore, we demonstrated that insulin-like growth factor 2 receptor (IGF2R) was among the target genes of miR-143-3p by searching 3 widely used bioinformatics databases and preliminary validation. Our experiments suggest that knockdown of circulating miR-143-3p may protect against insulin resistance in the setting of MetS via targeting of IGF2R and activation of the insulin signaling pathway. Our results characterize the miR-143-3p-IGF2R pathway as a potential target for the treatment of obesity-associated insulin resistance.

Circulating fractalkine levels predict the development of the metabolic syndrome.

The fractalkine/CX3CR1 axis plays an important role in regulating glucose and lipid metabolism. However, the role of fractalkine in metabolic disorders remains to be fully elucidated. We selected 887 Chinese (40-65 years old) at baseline, with a subgroup of 459 participants examined again 2 years later. The relationship of serum fractalkine levels with the metabolic syndrome (MetS) and its components was investigated. At baseline, participants with MetS had higher fractalkine concentrations than their counterparts without MetS (P < 0.001). At the 2-year follow-up, participants in the highest quartile of baseline fractalkine exhibited higher values for body mass index, waist circumference, waist-to-hip ratio, body fat percentage, glucose, insulin, total cholesterol, triglycerides (TG), and homeostasis model assessment of insulin resistance (HOMA-IR) and lower value for high density lipoprotein-cholesterol (HDL-c) (all P < 0.05). Among 390 participants without MetS at baseline, 45 developed it at year 2. Even after multiple adjustments for visceral adipose tissue area, HOMA-IR, C-reactive protein (CRP), or TG and HDL-c, baseline fractalkine predicted the development of MetS (OR = 7.18, 95%CI: 2.28-18.59). In conclusion, circulating fractalkine predicts the development of the MetS independently of central obesity, CRP, insulin resistance, and dyslipidemia.