Bile acids are acknowledged as signaling molecules involved in metabolic syndrome. The Takeda G protein-coupled receptor 5 (TGR5) functions as a significant bile acid receptor. The accumulated evidence suggests that TGR5 involves lipid homeostasis, glucose metabolism, and inflammation regulation. In line with this, recent preclinical studies also demonstrate that TGR5 plays a significant role in the generation and progression of metabolic syndrome, encompassing type 2 diabetes mellitus, obesity, atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). In this review, we discuss the role of TGR5 in metabolic syndrome, illustrating the underlying mechanisms and therapeutic targets.

(1) Autophagy is an important biological process in cells and is closely associated with the development and progression of non-alcoholic fatty liver disease (NAFLD). Therefore, this study aims to investigate the biological function of the autophagy hub genes, which could be used as a potential therapeutic target and diagnostic markers for NAFLD. (2) Male C57BL/6J mice were sacrificed after 16 and 38 weeks of a high-fat diet, serum biochemical indexes were detected, and liver lobules were collected for pathological observation and transcriptome sequencing. The R software was used to identify differentially expressed autophagy genes (DEGs) from the transcriptome sequencing data of mice fed with a normal diet for 38 weeks (ND38) and a high-fat diet for 38 weeks (HFD38). Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed on the DEGs, a protein–protein interaction (PPI) network of the DEGs was established using the STRING data website, and the results were visualized through Cytoscape. (3) After 16 weeks and 38 weeks of a high-fat diet, there was a significant increase in body weight, serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and triglycerides (TG) in mice, along with lipid accumulation in the liver, which was more severe at 38 weeks than at 16 weeks. The transcriptome data showed significant changes in the expression profile of autophagy genes in the livers of NAFLD mice following a long-term high-fat diet. Among the 31 differentially expressed autophagy-related genes, 13 were upregulated and 18 were downregulated. GO and KEGG pathway analysis revealed that these DEGs were primarily involved in autophagy, cholesterol transport, triglyceride metabolism, apoptosis, the FoxO signaling pathway, the p53 signaling pathway and the IL-17 signaling pathway. Four hub genes were identified by the PPI network analysis, of which Irs2, Pnpla2 and Plin2 were significantly downregulated, while Srebf2 was significantly upregulated by the 38-week high-fat diet. (4) The hub genes Irs2, Pnpla2, Srebf2 and Plin2 may serve as key therapeutic targets and early diagnostic markers in the progression of NAFLD.

Objective: To explore the material basis and potential molecular mechanism of Gynostemma pentaphyllum’s hypolipidaemic effects. Methods: A hyperlipidaemic rat model was established to evaluate the hypolipidaemic effect of Gynostemma pentaphyllum. Next, we verified the bioactive components (BCI) and potential targets of Gynostemma pentaphyllum in the treatment of hyperlipidaemia using network pharmacology and molecular docking, and constructed the pharmacological network and PPI network. Then the core genes were enriched by GO and KEGG. Finally, the bioactive components were docked with the key targets to verify the binding ability between them.Results: The results showed that the serum TC, LDL-C and HDL-C levels were significantly decreased (P<0.05), the number of liver vacuoles was also significantly reduced and the relative expression of PPARγ and SOD mRNA increased (P>0.05) after gynostemma administration. What’s more, a total of 24 active ingredients and 125 common targets of the drug and the disease. PPI network and functional analysis showed that AKT1, TNF, IL6, VEGFA, EGFR, PPARG are very important which were mainly involved in the cancer pathway, the chemo-carcinogenesis-receptor activation pathway, the lipid and atherosclerosis pathway, proteoglycans in cancer, the PI3K-Akt signalling pathway. Molecular docking results showed that the core active components of gibberellin, gibberellin saponin XXVIII, 3'-methylrhodopsin and gibberellin showed good affinity with the Hub gene.Conclusion: Gynostemma has a significant hypolipidaemic effect and may affect lipid metabolism by acting on multiple targets through multiple components.