Atherosclerosis is a chronic and multifactorial inflammatory disease and is closely associated with cardiovascular and cerebrovascular diseases. circRNAs can act as competing endogenous RNAs to mRNAs and function in various diseases. However, there is little known about the function of circRNAs in atherosclerosis. In this study, three rabbits in the case group were fed a high-fat diet to induce atherosclerosis and another three rabbits were fed a normal diet. To explore the biological functions of circRNAs in atherosclerosis, we analyzed the circRNA, miRNA and mRNA expression profiles using RNA-seq. Many miRNAs, mRNAs and circRNAs were identified as significantly changed in atherosclerosis. We next predicted miRNA-target interactions with the miRanda tool and constructed a differentially expressed circRNA-miRNA-mRNA triple network. A gene ontology enrichment analysis showed that genes in the network were involved in cell adhesion, cell activation and the immune response. Furthermore, we generated a dysregulated circRNA-related ceRNAs network and found seven circRNAs (ocu-cirR-novel-18038, -18298, -15993, -17934, -17879, -18036 and -14389) were related to atherosclerosis. We found these circRNAs also functioned in cell adhesion, cell activation and the immune response. These results show that the crosstalk between circRNAs and their competing mRNAs might play crucial roles in the development of atherosclerosis.

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Either restricted or excessive sleep may impair semen quality. Further research is needed to validate this finding.

. Hydrogen sulfide reduces serum triglyceride by activating liver autophagy via the AMPK-mTOR pathway. Am J Physiol Endocrinol Metab 309: E925-E935, 2015. First published October 6, 2015; doi:10.1152/ajpendo.00294.2015.-Autophagy plays an important role in liver triglyceride (TG) metabolism. Inhibition of autophagy could reduce the clearance of TG in the liver. Hydrogen sulfide (H2S) is a potent stimulator of autophagic flux. Recent studies showed H2S is protective against hypertriglyceridemia (HTG) and noalcoholic fatty liver disease (NAFLD), while the mechanism remains to be explored. Here, we tested the hypothesis that H2S reduces serum TG level and ameliorates NAFLD by stimulating liver autophagic flux by the AMPK-mTOR pathway. The level of serum H2S in patients with HTG was lower than that of control subjects. Sodium hydrosulfide (NaHS, H2S donor) markedly reduced serum TG levels of male C57BL/6 mice fed a high-fat diet (HFD), which was abolished by coadministration of chloroquine (CQ), an inhibitor of autophagic flux. In HFD mice, administration of NaSH increased the LC3BII-to-LC3BI ratio and decreased the p62 protein level. Meanwhile, NaSH increased the phosphorylation of AMPK and thus reduced the phosphorylation of mTOR in a Western blot study. In cultured LO2 cells, high-fat treatment reduced the ratio of LC3BII to LC3BI and the phosphorylation of AMPK, which were reversed by the coadministration of NaSH. Knockdown of AMPK by siRNA in LO2 cells blocked the autophagic enhancing effects of NaSH. The same qualitative effect was observed in AMPK␣2 Ϫ/Ϫ mice. These results for the first time demonstrated that H2S could reduce serum TG level and ameliorate NAFLD by activating liver autophagy via the AMPKmTOR pathway. hydrogen sulfide; triglyceride; NAFLD; autophagy; AMPK HYPERTRIGLYCERIDEMIA (HTG) is the most common lipid metabolism disorder and is an important independent risk factor for cardiovascular and cerebrovascular diseases (2, 10, 29). The liver plays a cardinal role in lipid metabolism. Increased production and/or decreased clearance of triglyceride (TG) in the liver inevitably results in HTG (13, 30), while TG accumulation in the liver can lead to nonalcoholic fatty liver disease (NAFLD) (40). NAFLD is the most prevalent chronic liver disease in the developed world and is an important risk factor for the development of liver fibrosis and cirrhosis and predisposes to the development of hepatocellular carcinoma (1, 26).Recent research suggests that autophagy participates in the regulation of liver lipid metabolism (5, 33, 34). Autophagy modulates hepatocyte lipid metabolism through lipophagy, which involves sequestration of lipid drops in double-membrane autophagosomes, followed by fusion with lysosomes to form autolysosomes, and subsequent degradation of TG by lipases within the autolysosomes. Reduction of liver cell autophagic activity causes decreased lipolysis and provokes free fatty acid (FFA) ␤-oxidation, resulting in hepatic steatosis and often progresses to NAFLD and HTG (34).AMP-activated pro...

BACKGROUND AND PURPOSEAtrial metabolic remodelling is critical for the process of atrial fibrillation (AF). The PPAR-α/sirtuin 1 /PPAR co-activator α (PGC-1α) pathway plays an important role in maintaining energy metabolism. However, the effect of the PPAR-α agonist fenofibrate on AF is unclear. Therefore, the aim of this study was to determine the effect of fenofibrate on atrial metabolic remodelling in AF and explore its possible mechanisms of action. EXPERIMENTAL APPROACHThe expression of metabolic proteins was examined in the left atria of AF patients. Thirty-two rabbits were divided into sham, AF (pacing with 600 beats·min À1 for 1 week), fenofibrate treated (pretreated with fenofibrate before pacing) and fenofibrate alone treated (for 2 weeks) groups. HL-1 cells were subjected to rapid pacing in the presence or absence of fenofibrate, the PPAR-α antagonist GW6471 or sirtuin 1-specific inhibitor EX527. Metabolic factors, circulating biochemical metabolites, atrial electrophysiology, adenine nucleotide levels and accumulation of glycogen and lipid droplets were assessed. KEY RESULTSThe PPAR-α/sirtuin 1/PGC-1α pathway was significantly inhibited in AF patients and in the rabbit/HL-1 cell models, resulting in a reduction of key downstream metabolic factors; this effect was significantly restored by fenofibrate. Fenofibrate prevented the alterations in circulating biochemical metabolites, reduced the level of adenine nucleotides and accumulation of glycogen and lipid droplets, reversed the shortened atrial effective refractory period and increased risk of AF. CONCLUSION AND IMPLICATIONSFenofibrate inhibited atrial metabolic remodelling in AF by regulating the PPAR-α/sirtuin 1/PGC-1α pathway. The present study may provide a novel therapeutic strategy for AF. AbbreviationsAcAc, acetoacetate; AERP, atrial effective refractory period; AF, atrial fibrillation; BOH, β-hydroxybutyrate; FFA, free fatty acid; GLUT4, glucose transporter 4; GS1, glycogen synthase1; H-FABP, heart fatty acid binding protein; MCAD, medium-chain acylCoA dehydrogenase; mCPT-1, mitochondrial carnitine palmitoyltransferase1; PDH, pyruvate dehydrogenase; PDK4, pyruvate dehydrogenase kinase 4; PGC-1α, PPAR co-activator 1α; p-GS1, phosphorylated-GS1; TKB, total ketone body