N6-methyladenosine is a prevalent and abundant transcriptome modification, and its methylation regulates the various aspects of RNAs, including transcription, translation, processing and metabolism. The methylation of N6-methyladenosine is highly associated with numerous cellular processes, which plays important roles in the development of physiological process and diseases. The high prevalence of metabolic diseases poses a serious threat to human health, but its pathological mechanisms remain poorly understood. Recent studies have reported that the progression of metabolic diseases is closely related to the expression of RNA N6-methyladenosine modification. In this review, we aim to summarize the biological and clinical significance of RNA N6-methyladenosine modification in metabolic diseases, including obesity, type 2 diabetes, non-alcoholic fatty liver disease, hypertension, cardiovascular diseases, osteoporosis and immune-related metabolic diseases.

Diabetes mellitus is the leading chronic disease in the world, and diabetic nephropathy (DN) as one of its complications could increase the mortality. The development of DN is associated to abnormal hemodynamic factors like cytokine networks and the intervention of metabolic risk factors like blood pressure, blood glucose, and blood lipid. However, the pathogenesis of DN is still poorly understood. Although glucose-lowering drugs and insulins have significant effects on blood glucose, the fluctuation of blood glucose or other risk factors could continuously damage the kidney. Recent studies reported that the progression of DN is closely related to the expression of long noncoding RNA (lncRNA), which is important for the early diagnosis and targeted intervention of DN. In this review, we briefly summarize the published studies on the functions and potential mechanism of reported lncRNA in the regulation of DN.

Hyperuricemia is a risk factor for nonalcoholic fatty liver disease (NAFLD), however, the effect of gender on the hyperuricemia-related NAFLD development remains unclear. Here, we evaluated the clinical characteristics of NAFLD patients with hyperuricemia, and experimentally recapitulated this condition in male rats in order to gain insights on the possible impact of gender on the development of NAFLD in patients with hyperuricemia. The clinical characteristics of 238 NAFLD patients, together with the impacts of hyperuricemia on the major parameters related to the development of NALFD were analysed. In animal studies, NAFLD with hyperuricemia was induced in male SD rats using high-yeast high-fat diet containing potassium oxonate. The impact of uric acids on liver pathology, and the expression patterns of key molecules involved in the development of NAFLD, including silent information regulator 1 (SIRT1), nuclear factor kappa B subunit p65 (NF-κB p65), fork-head box class O-3a (FOXO3a), androgen receptor (AR), and xanthine oxidase (XO) were analysed. Male NAFLD patients with hyperuricemia displayed more frequent and extensive liver injury than those in female patients. In male rats, hyperuricemia was associated with increased levels of insulin, alanine aminotransferase (ALT) and triglyceride (TG). At the molecular level, hyperuricemia was associated with decreased expression of SIRT1 and its phosphorylation, phosphorylation of FOXO3a, increased expression of AR and XO, and deacetylation of NF-κB P65. Hyperuricemia is a compounding factor for NAFLD, particularly in males. The severer hepatic injury observed in male NAFLD patients may be attributed to the suppression of SIRT1 signalling induced by hyperuricemia.

Background Hyperuricemia is a recognised risk factor for the development of nonalcoholic fatty liver disease (NAFLD). This study aims to investigate the therapeutic effect of resveratrol (RES) on the treatment of hyperuricemia-related NAFLD in rats and the underlying mechanisms. Methods NAFLD with hyperuricemia was induced in rats using high-yeast high-fat diet containing potassium oxonate. The impact of RES on liver pathology, and the expression of silent information regulator 1 (SIRT1), fork-head box class O-3a (FOXO3a), and nuclear factor kappa B subunit p65 (NF-κB p65) was analysed. Results RES significantly improved liver histology and reversed serum biochemical abnormalities. At the molecular level, RES improved insulin resistance (IR), inhibited hepatic steatosis, reduced oxidative stress and liver inflammation, and these effects were likely mediated through SIRT1-mediated FOXO3a phosphorylation and NF-κB P65 deacetylation. Conclusions Resveratrol is a promising agent for the treatment of hyperuricemia-related NAFLD through activating SIRT1 pathways.

Objectives. Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) throughout the world, and the identification of novel biomarkers via bioinformatics analysis could provide research foundation for future experimental verification and large-group cohort in DN models and patients. Methods. GSE30528, GSE47183, and GSE104948 were downloaded from Gene Expression Omnibus (GEO) database to find differentially expressed genes (DEGs). The difference of gene expression between normal renal tissues and DN renal tissues was firstly screened by GEO2R. Then, the protein-protein interactions (PPIs) of DEGs were performed by STRING database, the result was integrated and visualized via applying Cytoscape software, and the hub genes in this PPI network were selected by MCODE and topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to determine the molecular mechanisms of DEGs involved in the progression of DN. Finally, the Nephroseq v5 online platform was used to explore the correlation between hub genes and clinical features of DN. Results. There were 64 DEGs, and 32 hub genes were identified, enriched pathways of hub genes involved in several functions and expression pathways, such as complement binding, extracellular matrix structural constituent, complement cascade related pathways, and ECM proteoglycans. The correlation analysis and subgroup analysis of 7 complement cascade-related hub genes and the clinical characteristics of DN showed that C1QA, C1QB, C3, CFB, ITGB2, VSIG4, and CLU may participate in the development of DN. Conclusions. We confirmed that the complement cascade-related hub genes may be the novel biomarkers for DN early diagnosis and targeted treatment.

Background. Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus and is a major cause of end-stage kidney disease. Cordyceps sinensis (Cordyceps, Dong Chong Xia Cao) is a widely applied ingredient for treating patients with DN in China, while the molecular mechanisms remain unclear. This study is aimed at revealing the therapeutic mechanisms of Cordyceps in DN by undertaking a network pharmacology analysis. Materials and Methods. In this study, active ingredients and associated target proteins of Cordyceps sinensis were obtained via Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Swiss Target Prediction platform, then reconfirmed by using PubChem databases. The collection of DN-related target genes was based on DisGeNET and GeneCards databases. A DN-Cordyceps common target interaction network was carried out via the STRING database, and the results were integrated and visualized by utilizing Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to determine the molecular mechanisms and therapeutic effects of Cordyceps on the treatment of DN. Results. Seven active ingredients were screened from Cordyceps, 293 putative target genes were identified, and 85 overlapping targets matched with DN were considered potential therapeutic targets, such as TNF, MAPK1, EGFR, ACE, and CASP3. The results of GO and KEGG analyses revealed that hub targets mainly participated in the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, PI3K-Akt signaling pathway, and IL-17 signaling pathway. These targets were correlated with inflammatory response, apoptosis, oxidative stress, insulin resistance, and other biological processes. Conclusions. Our study showed that Cordyceps is characterized as multicomponent, multitarget, and multichannel. Cordyceps may play a crucial role in the treatment of DN by targeting TNF, MAPK1, EGFR, ACE, and CASP3 signaling and involved in the inflammatory response, apoptosis, oxidative stress, and insulin resistance.