Dendropanax trifidus Sap-Mediated Suppression of Obese Mouse Body Weight and the Metabolic Changes Related with Estrogen Receptor Alpha and AMPK-ACC Pathways in Muscle Cells.

Ahreum Lee,Young Joo Lee,Soo Min Cho,Dalnim Kim,Hyun-Jeong Yang,Ik-Hyun Cho,Eugene Koh,Namkyu Lee

doi:10.3390/nu14051098

Abstract

Dendropanax trifidus (DT) is a medicinal herb native to East Asia, which has been used extensively for its therapeutic properties in traditional medicine. In this study, we examined the effects of DT sap on the regulation of body weight and muscle metabolism in mice. Obese model db/db mice were administered daily with DT sap or vehicle control over a 6-week period. The effects of DT sap on muscle metabolism were studied in C2C12 muscle cells, where glycolytic and mitochondrial respiration rates were monitored. As AMP-activated protein kinase (AMPK) is a master regulator of metabolism and plays an important function as an energy sensor in muscle tissue, signaling pathways related with AMPK were also examined. We found that DT sap inhibited body weight increase in db/db, db/+, and +/+ mice over a 6-week period, while DT sap-treated muscle cells showed increased muscle metabolism and also increased phosphorylation of AMPK and Acetyl-CoA Carboxylase (ACC). Finally, we found that DT sap, which is enriched in estrogen in our previous study, significantly activates estrogen alpha receptor in a concentration-dependent manner, which can drive the activation of AMPK signaling and may be related to the muscle metabolism and weight changes observed here.

Highlights

Decrease of energy expenditure can increase body weight [1,2]
We did not find a significant change in food or water consumption by Dendropanax trifidus (DT) sap administration (Supplementary Figure S1), DT sap-injected mice exhibited a suppression of body weight increase
In order to examine whether DT sap changes the energy expenditure of muscle cell, we investigated the changes in the glyco lytic and mitochondrial function of C2C12 murine muscle cells treated with various con centrations of DTsap (Agilent Seahorse XF system, see Methods), (Figures 2,3)

Summary

Introduction

Decrease of energy expenditure can increase body weight [1,2]. A person with lower metabolic rate gains more weight under the same caloric intake. The skeletal muscle is the largest metabolic organ system in the body [3]. It comprises ~40% of body weight in non-obese individuals [4] and is responsible for 20~30% of total resting oxygen uptake [4,5]. Skeletal muscle metabolism is an important determinant for wholebody resting metabolic rate [6], and changes dramatically depending on exercise activity. Skeletal muscle ATP consumption increases, followed by increase in intracellular AMP concentrations, resulting in increases in the ratios of AMP/ATP and ADP/ATP, and leading to the activation of AMP-activated protein kinase (AMPK) [7]

Objectives

Methods

Results

Conclusion