ABSTRACT
Background: The majority of chronic liver disease is caused by non-alcoholic fatty liver disease (NAFLD), which is one of the highly prevalent diseases worldwide. The current studies have found that non-coding RNA (ncRNA) plays an important role in the NAFLD, but few studies on circRNA. In this study, genes, microRNA (miRNA), and circular RNA (circRNA) associated with NAFLD were found by bioinformatic methods, bringing a novel perspective for the prevention and treatment of NAFLD. Methods: Expression data of GSE63067 was acquired from Gene Expression Omnibus (GEO) database. The liver samples were collected from the people diagnosed with NAFLD or not. Differentially expressed genes (DEGs) were obtained from the steatosis vs. the control group and non-alcoholic steatohepatitis (NASH) vs. the control group using the GEO2R online tool. The overlapping genes remained for further functional enrichment analysis and protein-protein interaction network analysis. MiRNAs and circRNAs targeting these overlapping DEGs were predicted from the databases. Finally, the GSE134146 dataset was used to verify the expression of circRNA. Results: In summary, 228 upregulated and 63 downregulated differential genes were selected. The top 10 biological processes and relative signaling pathways of the upregulated differential genes were obtained. Also, ten hub genes were performed in the Protein-protein interaction (PPI) network. One hundred thirty-nine miRNAs and 902 circRNAs were forecast for the differential genes by the database. Ultimately, the crosstalk between hsa_circ_0000313, miR-6512-3p, and PEG10 was constructed. Conclusion: The crosstalk of hsa_circ_0000313-hsa-miR-6512-3p-PEG10 and some related non-coding RNAs may take part in NAFLD's pathogenesis, which could be the potential biomarkers of NAFLD in the future.
ABSTRACT
Bariatric surgery is the most common and effective treatment of severe obesity; however, these bariatric procedures always result in detrimental effects on bone metabolism by underlying mechanisms. This study aims to investigate the skeletal response to bariatric surgery and to explore whether Clostridium butyricum alleviates gut microbiota alteration-induced bone loss after bariatric surgery. Consequently, male SD rats received Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) surgery, respectively, followed by body weight recording. The bone loss after bariatric surgery was further determined by dual-energy X-ray absorptiometry (DXA), micro-CT measurement, histologic analyses, and Western blot. Besides, 16S rDNA gene sequencing was performed to determine the gut microbiota alteration after surgery, and intervention with fecal microbiota from RYGB donor was conducted in obese SD rats, followed by C. butyricum administration. Accordingly, rats in the RYGB and SG groups maintained sustained weight loss, and DXA and micro-CT measurement further demonstrated significant bone loss after bariatric surgery. Besides, histologic and Western blot analyses validated enhanced osteoclastogenesis and inhibited osteoblastogenesis and defective autophagy after surgery. The 16S rDNA gene sequencing suggested a significant alteration of gut microbiota composition in the RYGB group, and intervention with fecal microbiota from RYGB donor further determined that this kind of alteration contributed to the bone loss after RYGB. Meanwhile, C. butyricum might protect against this postoperative bone loss by promoting osteoblast autophagy. In summary, this study suggests novel mechanisms to clarify the skeletal response to bariatric surgery and provides a potential candidate for the treatment of bone disorder among bariatric patients. SIGNIFICANCE STATEMENT: The significance of this study is the discovery of obvious bone loss and defective autophagy after bariatric surgery. Besides, it is revealed that gut microbiota alterations could be the reason for impaired bone mass after bariatric surgery. Furthermore, Clostridium butyricum could alleviate the gut microbiota alteration-induced bone loss after bariatric surgery by promoting osteoblast autophagy.
