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ZishenWan reduces obesity in db/db mice by inhibiting p21 expression in adipose tissues
You Wu1,2,3, Huizhao Qin1,2,4, Zhiwei Qi1,2
1Key Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, 102488, China.
Background:
Obesity is a major risk factor for metabolic disorders, including type 2 diabetes, metabolic syndrome, and cardiovascular diseases. Recent studies suggest that adipocyte cell cycle regulation is linked to metabolic dysfunction, making cell cycle regulatory factors potential therapeutic targets. ZishenWan (ZSW), a traditional Chinese medicinal formula composed of three herbs, has shown therapeutic potential against diabetes and obesity. This study aimed to investigate the mechanisms underlying the weight-regulatory effects of ZSW.
Methods:
ZSW was orally administered to db/db mice for 5 weeks, with metformin used as a positive control. Body weight and fasting blood glucose levels were monitored weekly, and an oral glucose tolerance test was conducted at the end of the intervention. Insulin levels and serum lipid profiles were also assessed. Histological analysis was performed on adipose tissue, and epididymal adipose tissue (EAT) samples were collected for transcriptomic analysis. The findings from transcriptomic analysis were further validated using qPCR, immunohistochemistry, and western blotting.
Results:
ZSW significantly reduced body weight, inhibited adipocyte hypertrophy, and improved insulin sensitivity and insulin secretion in db/db mice without affecting liver or kidney function. Transcriptomic analysis revealed that ZSW altered the expression of genes involved in lipid metabolism and inhibited p21 expression. Additionally, ZSW activated the PI3K/AKT/FoxO1 signaling pathway, resulting in reduced p21 expression, increased apoptosis, and enhanced UCP1 expression in EAT.
Conclusions:
ZSW may improve obesity-related metabolic disorders by activating the PI3K/AKT pathway and downregulating p21 expression in EAT. These effects promote adipocyte apoptosis, enhance thermogenesis, inhibit adipocyte hypertrophy, and improve insulin sensitivity.
Insights
ZishenWan (ZSW) reduces body weight and improves metabolic health in obese mice by activating the PI3K/AKT pathway. This traditional Chinese medicine enhances adipocyte apoptosis and thermogenesis, offering a potential therapeutic strategy for obesity-related disorders.
Area of Science:
- Metabolic research
- Pharmacology
- Traditional Chinese Medicine
Background:
- Obesity is a significant risk factor for type 2 diabetes, metabolic syndrome, and cardiovascular diseases.
- Adipocyte cell cycle regulation is increasingly recognized as a factor in metabolic dysfunction.
- ZishenWan (ZSW), a traditional Chinese medicinal formula, has demonstrated potential in treating diabetes and obesity.
Purpose of the Study:
- To investigate the underlying mechanisms of ZSW's weight-regulatory effects.
- To explore ZSW's impact on adipocyte biology and metabolic pathways in obese mice.
Main Methods:
- Oral administration of ZSW to db/db mice for 5 weeks, with metformin as a positive control.
- Monitoring of body weight, fasting blood glucose, insulin levels, and serum lipid profiles.
- Transcriptomic analysis of epididymal adipose tissue (EAT), validated by qPCR, immunohistochemistry, and western blotting.
Main Results:
- ZSW significantly reduced body weight and adipocyte hypertrophy while improving insulin sensitivity and secretion.
- Transcriptomic analysis indicated ZSW altered lipid metabolism gene expression and inhibited p21 expression.
- ZSW activated the PI3K/AKT/FoxO1 pathway, leading to decreased p21, increased apoptosis, and enhanced UCP1 expression in EAT.
Conclusions:
- ZSW may ameliorate obesity-related metabolic disorders through PI3K/AKT pathway activation and p21 downregulation in EAT.
- These actions promote adipocyte apoptosis, enhance thermogenesis, reduce hypertrophy, and improve insulin sensitivity.
