MicroRNA-30b regulates insulin sensitivity by targeting SERCA2b in non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Insulin resistance is strongly associated with non-alcoholic fatty liver disease, a chronic, obesity-related liver disease. Increased endoplasmic reticulum (ER) stress plays an important role in the development of insulin resistance. In this study, we investigated the roles of miRNAs in regulating ER stress in the liver of rats with obesity. METHODS: We used miRNA microarray to determine the miRNA expression profiles in the liver of rats fed with a high fat diet (HFD). We used prediction algorithms and luciferase reporter assay to identify the target gene of miRNAs. To overexpress the miRNA miR-30b or inhibit miR-30b rats were injected with lentivirus particles containing PGLV3-miR-30b or PGLV3-miR-30b antimiR through tail vein. Hepatic steatosis was measured using transient elastography in human subjects. RESULTS: Our data showed that miR-30b was markedly up-regulated in the liver of HFD-treated rats. Bioinformatic and in vitro and in vivo studies led us to identify sarco(endo)plasmic reticulum Ca2+ -ATPase 2b (SERCA2b), as a novel target of miR-30b. Overexpression of miR-30b induced ER stress and insulin resistance in rats fed with normal diet, whereas inhibition of miR-30b by miR-30b antimiR suppressed ER stress and insulin resistance in HFD-treated rats. Finally, our data demonstrated that there was a positive correlation between serum miR-30b levels and hepatic steatosis or homoeostasis model assessment of insulin resistance (HOMA-IR) in human subjects. CONCLUSIONS: Our findings suggest that miR-30b represents not only a potential target for the treatment of insulin resistance, but also a non-invasive disease biomarker of NAFLD.

Effects of complete Freund's adjuvant on immunohistochemical distribution of IL-1beta and IL-1R I in neurons and glia cells of dorsal root ganglion.

AIM: To investigate the effects of complete Freund adjuvant (CFA) on inflammatory hyperalgesia and morphological change of the coexistence of interleukin-1 beta (IL-1beta) and type I IL-1 receptor (IL-1RI) in neurons and glia cells of rat dorsal root ganglion (DRG). METHODS: The pain-related parameters and the expression of IL-1RI and IL-1beta positive neurons and glia cells of DRG in normal saline (NS) and adjuvant-induced arthritic (AA) group were examined with pain behavior assessment methods and immunohistochemical assay, respectively. RESULTS: Five hours, 1 d, and 2 d after intra-articular injection of 50 microL CFA, tactile hyperalgesia induced by CFA was observed in the foot flexion and extension scores of the ipsilateral hindpaw of AA group. Three days after injection, the distribution of IL-1RI/IL-1beta double-stained coexisted neurons and glia cells were observed in ipsilateral DRG of both groups. The number of IL-1beta positive neurons, IL-1RI positive neurons, IL-1beta/IL-1RI double-stained neurons, and IL-1RI positive glia cells in ipsilateral DRG of the AA group were higher than that of NS group (P<0.05 or P<0.01). CONCLUSION: The coexistence of IL-1beta and IL-1RI in neurons and nonneuronal cells suggests an as yet unknown autocrine and/or paracrine function of IL-1beta in the DRG. The function was enhanced in articular arthritis induced by CFA and could play an important role in hyperalgesia under inflammatory conditions.