# Anti-obesity effects of Wumeishanzhayin: an integrated lipidomics and transcriptomics study

## TL;DR

This study shows that Wumeishanzhayin (WMSZY) reduces obesity and improves metabolism in mice by regulating lipid pathways, particularly through the AMPK/CPT-1 signaling pathway.

## Contribution

The study integrates lipidomics and transcriptomics to reveal WMSZY's anti-obesity mechanisms, particularly its regulation of the AMPK/CPT-1 pathway.

## Key findings

- WMSZY reduced body weight gain and improved lipid and glucose metabolism in HFHF diet-induced mice.
- Lipidomics and transcriptomics linked WMSZY's effects to cholesterol metabolism, adipocyte lipolysis, and AMPK signaling.
- Molecular docking and experimental validation confirmed AMPK/CPT-1 pathway activation by WMSZY metabolites.

## Abstract

The global prevalence of adult obesity has increased significantly, affecting over 890 million adults worldwide. Wumeishanzhayin (WMSZY), a formulation derived from four medicinal and edible botanical drugs, has shown efficacy in alleviating obesity and lipid metabolism disorders induced by high-fat and high-fructose (HFHF) diets. However, its underlying therapeutic mechanisms remain unclear.

This study aims to investigate the therapeutic effects and mechanisms of WMSZY in ameliorating obesity induced by a HFHF diet.

UPLC-MS/MS was used to characterize the metabolites of WMSZY. The effects of WMSZY on body weight gain, lipid metabolism, and glucose dysfunction were evaluated in a HFHF diet-induced murine model. Targeted lipidomics and transcriptomics analyses were performed to identify differentially altered lipids (DALs) and differentially expressed genes (DEGs). Computational approaches, including molecular docking simulation and dynamics simulations, were used to predict bioactive compound-target interactions. Key findings were validated through RT-qPCR and Western blot. Integrated transcriptomic and lipidomic analyses identified potential therapeutic targets.

Sixteen metabolites were identified in WMSZY. Animal studies showed that WMSZY reduced body weight gain, improved lipid and glucose metabolism, and alleviated inflammation in HFHF diet-induced mice. Targeted lipidomics indicated that WMSZY’s anti-obesity effect may be linked to cholesterol metabolism, adipocyte lipolysis, lipid digestion, insulin resistance, and glycerolipid metabolism. Transcriptomic analysis suggested involvement of AMPK, MAPK, and PPAR signaling pathways. Molecular docking simulation revealed strong binding of WMSZY metabolites with AMPK, and simulations showed that cryptochlorogenic acid had notable binding affinity. The data from Western blot and RT-qPCR showed changes associated with the activation of the AMPK/CPT-1 pathway and the inhibition of lipid metabolism-related genes following WMSZY treatment.

WMSZY significantly reduces body weight gain and ameliorates glucose and lipid metabolic disorders in HFHF diet-induced mice. Its anti-obesity effect is likely due to the regulation of lipid metabolism via the AMPK/CPT-1 signaling pathway.

The image is a triptych depicting a study on WMSZY's effects on obesity. The first panel shows graphs and mouse model photos indicating improved obesity indicators with WMSZY treatment. The middle panel explores mechanisms through lipidomics and transcriptomics, using charts and Venn diagrams to illustrate changes. The final panel verifies results with molecular graphics, Western blotting results, and bar graphs demonstrating WMSZY's impact at the molecular level.