Abstract
Obesity is a chronic metabolic disease caused by genetic and environmental factors that has become a serious global health problem. There is evidence that gut microbiota is closely related to the occurrence and development of obesity. Erchen Decoction (ECD), a traditional Chinese medicine, has been widely used for clinical treatment and basic research of obesity and related metabolic diseases in recent years. It can significantly improve insulin resistance (IR) and lipid metabolism disorders. However, there is no microbiological study on its metabolic regulation. In this study, we investigated the effects of ECD on obesity, especially lipid metabolism and the composition and function of gut microbiota in Zucker diabetic fatty (ZDF) rats, and explored the correlation between the biomarkers of gut microbiota and metabolite and host phenotype. The results showed that ECD could reduce body weight, improve IR and lipid metabolism, and reduce the concentration of free fatty acids (FFA) released from white adipose tissue (WAT) due to excessive lipolysis by interfering with the insulin receptor substrate 1 (IRS1)/protein kinase B (AKT)/protein kinase A (PKA)/hormone-sensitive triglyceride lipase (HSL) signaling pathway in ZDF rats. Additionally, ECD gradually adjusted the overall structure of changed gut microbiota, reversed the relative abundance of six genera, and changed the function of gut microbiota by reducing the content of propionic acid, a metabolite of gut microbiota, in ZDF rats. A potentially close relationship between biomarkers, especially Prevotella, Blautia, and Holdemania, propionic acid and host phenotypes were demonstrated through correlation analysis. The results suggested that the beneficial effects of ECD on obesity, especially lipid metabolism disorders, are related to the regulation of gut microbiota in ZDF rats. This provides a basis for further research on the mechanism and clinical application of ECD to improve obesity via gut microbiota.
Highlights
With the improvement of living standards and changes in lifestyles, the number of obese people is increasing sharply
Consistent with previous results, we found that adipocytes expanded, insulin receptor substrate 1 (IRS1) phosphorylation increased, AKT activity decreased, and insulin signal transduction was impaired, while protein kinase A (PKA)-mediated hormone-sensitive triglyceride lipase (HSL) activity was upregulated and the ability to release free fatty acids (FFA) into the circulation was enhanced in the white adipose tissue (WAT) of Zucker diabetic fatty (ZDF) rats
We found that Erchen Decoction (ECD) intervention reduced the elevated Prevotella in ZDF rats, and in addition to insulin resistance, Prevotella abundance was markedly positively correlated with lipid metabolism disorders, while previous studies focused on carbohydrate and amino acid metabolic pathways (Petersen et al, 2017)
Summary
With the improvement of living standards and changes in lifestyles, the number of obese people is increasing sharply. The latest data has showed that, there were more than 1.9 billion adults worldwide who were overweight (about 39% of the total), and 650 million who were obese (about 13% of the total). 38 million children under the age of five were overweight or obese. GRAPHICAL ABSTRACT | Erchen Decoction could inhibit excessive lipolysis and improve lipid metabolism disorders by regulating the IRS1/AKT/PKA/HSL signaling pathway in white adipose tissue of ZDF rats. The delay in developing obesity was related to changes in gut microbiota composition and function in ZDF rats. How to effectively prevent obesity and reduce the occurrence and development of related diseases has become a major research focus
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