Tangzhiping Decoction Improves Glucose and Lipid Metabolism and Exerts Protective Effects Against White Adipose Tissue Dysfunction in Prediabetic Mice

Abstract

Background

Prediabetes, characterized by a series of metabolic abnormalities, increases the risk of diabetes and cardiovascular diseases. Tangzhiping (TZP), a clinically validated traditional Chinese medicine formula, is used to treat impaired glucose tolerance. However, the underlying mechanism of TZP in intervening prediabetes is not fully elucidated.

Purpose

The current study aimed to evaluate the protective effect of TZP against prediabetes mice and explore its potential mechanism.

Methods

After establishing a prediabetic animal model through 12 weeks of high-fat diet (HFD) feeding, mice were subjected to TZP for 8 weeks. Various parameters related to body weight, glucose and lipid metabolism, and insulin sensitivity were measured. Histopathological examinations observed adipose cell size and liver lipid deposition. The Sable Promethion system assessed energy metabolism activity. Transcriptomic analysis of Epididymal white adipose tissue (EWAT) identified enriched pathways and genes. The key genes in the enriched pathways were identified through RT-PCR.

Results

Our data revealed that the administration of TZP reduced body weight and fat mass in a prediabetes mouse model. TZP normalized the glucose and insulin levels, improved insulin resistance, and decreased plasma TC and FFA. The alleviation of adipose tissue hypertrophy and lipid deposition by TZP was demonstrated through pathological examination. Indirect calorimetry measurements indicated a potential increase in VO₂ and EE levels with TZP. The results of EWAT transcription showed that TZP reversed pathways and genes related to inflammation and catabolic metabolism. RT-PCR demonstrated that the mRNA expression of inflammation and lipolysis, including Tlr2, Ccr5, Ccl9, Itgb2, Lipe, Pnpla2, Cdo1, Ces1d, Echs1, and Acad11, were changed by TZP treatment.

Conclusion

TZP effectively alleviates obesity, impaired glucose and lipid metabolism, and insulin resistance. The effect of TZP might be associated with the regulation of gene expression in dysfunctional adipose tissue.

Graphical Abstract

Keywords:

• traditional Chinese medicine
• Tangzhiping
• prediabetes
• adipose tissue
• inflammation
• lipolysis

Ethical Statement

All animal experiments were approved by the Animal Ethics Committee of the Capital Medical University (NO. AEEI-2022-022) and performed in accordance with the Guide for the Care and Use of Laboratory Animals of the Beijing Municipal Government.

Acknowledgments

The authors gratefully acknowledge the financial support from National Key R&D Program of China (No. 2018YFC1704102) and National Natural Science Foundation of China (No. 81302950).

Disclosure

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.