ABSTRACT
Background: Nonalcoholic fatty liver disease (NAFLD) is the most frequent cause of chronic liver diseases worldwide. At present, there are no effective pharmacological therapies for NAFLD except lifestyle intervention-mediated weight loss. Atractylenolide III (ATL III), the major bioactive component found in Atractylode smacrocephala Koidz, has been shown to exert anti-oxidant, anti-tumor, anti-allergic response, anti-bacterial effects and cognitive protection. Here we investigate the therapeutic potential and underlying mechanisms of ATL III for the treatment of NAFLD. Methods: Male C57BL/6J mice were fed a high-fat diet (HFD) and treated with ATL III. Lipid accumulation was analyzed by Oil Red O staining in liver tissues and free fatty acids (FFAs)-treated hepatocytes. AMP-activated protein (AMPK) and sirtuin 1(SIRT1) signaling pathways were inhibited by Compound C and EX527 in vitro, respectively. Small-interfering RNA (siRNA) was used to knockdown adiponectin receptor 1 (AdipoR1) expression in HepG2 cells. Results: ATL III treatment ameliorated liver injury and hepatic lipid accumulation in the HFD-induced NAFLD mouse model as demonstrated by that ATL III administration significantly reduced serum levels of alanine aminotransferase, glutamic oxaloacetic transaminase, triglycerides, total cholesterol and low-density lipoprotein. Furthermore, treatment with ATL III alleviated hepatic oxidative stress, inflammation and fibrosis in the HFD feeding model. To study the underlying mechanisms, we performed Computer Aided Design assay and found that open-formed AdipoR1 and adiponectin receptor 2 were the potential receptors targeted by ATL III. Interestingly, HFD feeding or FFAs treatment only reduced hepatic AdipoR1 expression, while such reduction was abolished by ATL III administration. In addition, in vitro treatment with ATL III activated the AdipoR1 downstream AMPK /SIRT1 signaling pathway and reduced lipid deposition in HepG2 cells, which was diminished by silencing AdipoR1. Finally, inhibition of AMPK or SIRT1, the AdipoR1 downstream signaling, abolished the protective effects of ATL III on lipid deposition and oxidative stress in FFAs-treated HepG2 cells. Conclusion: Our findings suggest that ATL III is a therapeutic drug for the treatment of NAFLD and such protective effect is mediated by activating hepatic AdipoR1-mediated AMPK/SIRT1 signaling pathway.
Subject(s)
Non-alcoholic Fatty Liver Disease , AMP-Activated Protein Kinases/metabolism , Animals , Diet, High-Fat/adverse effects , Hep G2 Cells , Humans , Lactones , Lipid Metabolism , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/metabolism , Receptors, Adiponectin/metabolism , Sesquiterpenes , Sirtuin 1/metabolism , Triglycerides/metabolismABSTRACT
This study was designed to examine the prevalence and the risk factors of poor sleep quality in 4318 incoming university students in Taiwan. The test battery comprised a self-administered structured questionnaire, including items related to personal medical history and lifestyle habits, the Measurement of Support Functions (MSF), Pittsburgh Sleep Quality Index (PSQI), Chinese Internet Addiction Scale-Revision (CIAS-R), neuroticism subscale of the Maudsley Personality Inventory (MPI), and the 12-item Chinese Health Questionnaire (CHQ-12). Of the total study population, 2360 students (54.7%) were classified into the poor sleep quality group, as defined by a PSQI score ≥6. Based on the results of multivariate logistic regression analysis, poor sleep quality was significantly associated with undergraduate students, female gender, skipping breakfast, tea drinking, a higher tendency toward internet addition, poor social support, higher neuroticism, and higher CHQ scores. Poor sleep quality is prevalent among incoming university students in Taiwan, and more work is needed on the identification of the factors influencing poor sleep, and in providing systematic education in the importance of sleep and time management skills to university students.
