BACKGROUND Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease, can progress into nonalcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. Bile acids such as ursodeoxycholic acid (UDCA) play an essential role in the pathogenesis of NAFLD by regulating the level of sterol regulatory element-binding protein (SREBP) 1c, but the underlying regulatory mechanism remains elusive. Increased evidence indicates that the AKT/mTOR/SREBP-1 signaling pathway is a key pathway to regulate hepatic cellular lipid metabolism. UDCA may regulate the AKT/mTOR/SREBP-1 signaling pathway to ameliorate hepatic lipid metabolism. AIM To investigate the functional mechanism of UDCA in an oleic acid (OA)-induced cellular model of NAFLD. METHODS The cellular model of NAFLD was established using OA and treated with UDCA. First, the best concentration of UDCA was selected. For the best time-dependent assay, cells were stimulated with OA only or co-treated with OA and 2 mmol/L UDCA for 24 h, 48 h, and 72 h. Oil red O staining was used to observe the accumulation of intracellular lipids, while the intracellular contents of triglyceride, alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), and aspartate aminotransferase (AST) were detected by enzymatic methods. Meanwhile, the expression levels of AKT/mTOR/SREBP-1 signaling pathway-related proteins were detected by real-time PCR and Western blot. RESULTS In the NAFLD cell model established with LO2 cells induced using OA, lipid accumulation was obvious. UDCA significantly inhibited lipid accumulation at different concentrations (especially 2 mmol/L) and decreased cell growth ability at different time points. The biochemical parameters like ALT, AST, and GGT were significant improved by UDCA. UDCA treatment vividly repressed the activation of AKT, mTOR, and CRTC2 and the expression of nSREBP-1 in LO2 cells induced with OA. CONCLUSION Our findings demonstrate the effect of UDCA in improving NAFLD. UDCA attenuates OA-induced hepatic steatosis mainly by regulation of AKT/mTOR/SREBP-1 signal transduction.

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Our aim was to investigate whether human insulin (HI) or insulin glargine treatment could promote the proliferation of thyroid cells and determine the association between type 2 diabetes and thyroid disease. Rats were treated with different doses of HI and insulin glargine. Plasma glucose and the phosphorylation levels of the insulin receptor (IR), insulin-like growth factor 1 receptor (IGF-1R), protein kinase B (Akt), and extracellular signal-regulated kinase 1/2 (ERK1/2) were measured. A total of 105 rats were randomly assigned to three groups as follows: control group, HI group, and glargine group. Both drugs promoted the phosphorylation of IR, Akt, and ERK1/2 in a dose-dependent manner ( p < 0.05), and the effect of glargine persisted for longer period. Treatment with ultra-therapeutic doses of HI or glargine ( p < 0.05) increased the expression of Ki-67 in thyroid cells. The results demonstrated that therapeutic doses of glargine have a longer-lasting hypoglycemic control than HI. Based on the results, HI or glargine did not stimulate thyroid cell proliferation at therapeutic doses, but high doses did.

Nonalcoholic fatty liver disease (NAFLD) develops rapidly in high-fat diet (HFD) fed Mongolian gerbil ( Meriones unguiculatus). Here, we aim to explore the gene expression characteristics of Mongolian gerbil to better understand the underlying mechanism in this animal model. Mongolian gerbils were fed with normal diet or HFD for different periods. High-throughput sequencing was carried out on the hepatic mRNA and bioinformatics analysis was further performed. Eight hub genes Cd44, App, Cdc42, Cd68, Cxcr4, Csf1r, Adgre1, and Fermt3, which were involved in inflammation, fibrosis, and HCC were obtained. Four significant independent poor prognostic factors for HCC (GPC1, ARPC1B, DAB2, and CFL1) were screened out. qRT-PCR result showed that the above genes expressed high levels in different periods of modeling process. The findings of this study provide useful information for further studies on Mongolian gerbil NAFLD model.