Integrated hepatic transcriptome and metabolome reveal the mechanisms of Jiangtang Tiaozhi formula on improving glycolipid metabolic disorder.

Abstract

Background: Glycolipid metabolic disorder includes a series of chronic diseases that are closely associated with disturbances in both glucose and lipid metabolism. Jiangtang Tiaozhi formula (JTTZF) demonstrating significant hypoglycemic, lipid-modifying, and anti-inflammatory effects. However, the specific molecular mechanisms underlying JTTZF's hepatoprotective effects and its ability to ameliorate glycolipid metabolic disorder remain largely unexplored.

Aim: To investigate how JTTZF improves glycolipid metabolic disorder using hepatic transcriptome and metabolome analyses.

Methods: To induce glycolipid metabolic disorder, male C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks, after which they received an 8-week administration of JTTZF. Liver tissues were analyzed using transcriptomics and metabolomics. Real-time quantitative polymerase chain reaction validated key gene expression.

Results: Metabolomics data revealed that JTTZF significantly regulated HFD-induced alterations in glycolipid metabolism, with notable changes in pathways such as the pentose phosphate pathway, steroid hormone biosynthesis, and purine metabolism. Transcriptomics profiles indicated that JTTZF exerted regulatory effects on lipid and glucose metabolism, primarily through pathways including peroxisome proliferators-activated receptor signaling, drug metabolism other enzymes, and regulation of lipolysis in adipocytes. Real-time quantitative polymerase chain reaction confirmed that JTTZF modulated pivotal genes associated with fatty acid synthesis, lipolysis, insulin resistance, energy metabolism, and inflammation. These findings suggest that JTTZF may act through multiple pathways to improve glycolipid metabolic disorder.

Conclusion: JTTZF can ameliorate the glycolipid metabolic disorder induced by HFD-diet by regulating lipid metabolism and improving insulin tolerance.