Background MicroRNAs (MiRNAs) are known to participate in preadipocyte differentiation, but the manner in which miR-146a-5p participates in this process remains unclear. This study was performed to examine the participation of miR-146a-5p in 3T3-L1 cell differentiation. Material and Methods miR-146a-5p expression was upregulated and down-regulated to examine effects on 3T3-L1 cell differentiation. Bioinformatics analysis was performed to predict its target genes, and the signaling pathway it regulates was identified by qRT-PCR and Western blotting. The expression of miR-146a-5p in epididymal adipose tissue from obese mice and in an obese mouse adipose cell model was examined by qRT-PCR. Results 3T3-L1 cells differentiated into mature adipocytes successfully, as verified by increased areas of intracellular lipid droplets and elevated expression of mature adipocyte markers, and these cells had elevated miR-146a-5p expression. The intracellular lipid droplet and triglyceride contents and the expression of mature adipocyte markers were significantly increased in miR-146a-5p–overexpressing 3T3-L1 cells and markedly decreased in miR-146a-5p–inhibited 3T3-L1 cells. ErbB4 was a predicted target gene of miR-146a-5p. In miR-146a-5p–overexpressing 3T3-L1 cells, ErbB4 expression and ERK1/2 phosphorylation were decreased and the expression of PPAR-γ was increased; the opposite was observed in miR-146a-5p–inhibited 3T3-L1 cells. In addition, miR-146a-5p expression was significantly increased in the mouse epididymal adipose tissue and adipose cell model. Conclusions Upregulated miR-146a-5p expression was related to 3T3-L1 cell differentiation. MiR-146a-5p promoted 3T3-L1 cell differentiation by targeting ErbB4 and via the ERK1/2/PPAR-γ signaling pathway.

Background Green algae contain many polysaccharides. However, there is no information on whether Chaetomorpha linum polysaccharides (CLP) can modulate lipid and glucose metabolism. Material and methods CLP were extracted from chlorella and their components were characterized. Male C57BL/6 mice were randomized and provided with control chow as the control, or high fat diet (HFD) to induce nonalcoholic fatty liver disease (NAFLD). NAFLD mice were treated orally with water as the HFD group or with 50 or 150 mg/kg CLP daily for 10 weeks. The impact of CLP treatment on lipid and glucose metabolism and the PPARα signaling was examined by histology, Western blotting and biochemistry. Results CLP mainly contained arabinogalactan sulfate. Compared with the control, HFD feeding increased body weights, lipid droplet liver deposition and induced hyperlipidemia, liver functional impairment and glucose intolerance in mice. Treatment with CLP, particularly with a higher dose of CLP, limited the HFD-increased body weights and liver lipid droplet deposition, mitigated the HFD-induced hyperlipidemia and improved liver function and glucose tolerance in mice. Mechanistically, feeding with HFD dramatically decreased the expression of liver PPARα, CPT-1, and MCAD, but treatment with CLP enhanced their expression in a trend of dose-dependent in mice. Conclusions These findings indicated that CLP treatment alleviated the gain in body weights, NAFLD, and glucose intolerance in mice after HFD feeding by enhancing the PPARα/CPT-1/MCAD signaling.

Nonalcoholic fatty liver disease (NAFLD) is a multifactorial metabolic syndrome which could develop into hepatocellular carcinoma (HCC). Exosomes could mediate intercellular communications and play key roles in the occurrence and development of many diseases including NAFLD and HCC. However, expressions and roles of the genes related to exosomes in NAFLD-related HCC remain unclear. The objective of this study was to investigate the expressions and diagnostic values of exosome-related genes in NAFLD-related HCC. Firstly, we identified 15 genes related to exosome secretion by database searching. Two subgroups of patients with NAFLD-related HCC from GEO database were identified on the basis of exosome-related genes. High level of memory CD4 + T cells and low expressions of Immune Checkpoint genes were observed in the group with highly expressed genes which could promote exosome secretion. Subsequently, the logistic regression analysis was used to generate the formula based on three selected exosome-related genes in NAFLD-related HCC cohort. Receiver operating characteristic (ROC) curve analysis confirmed the good predictive power of formula. Functional analysis showed abundant metabolism-related pathways were screened out in DEGs between the high and low risk-score groups. The risk score from the formula was also positively correlated with memory CD4 + T cells and negatively associated with Immune Checkpoint genes. Finally, prognostic potential of the Exosome-related formula was analyzed in HCC cohort from TCGA database, and patients in the group with highly expressed exosome-promoted genes showed significantly reduced overall survival. We also constructed a nomogram to improve the predictive value of the formula for evaluating the prognosis of patients with HCC. In summary, our study clarified the significance of exosome-related genes in the development of NAFLD-related HCC.