Anti-adipogenic effects of viscothionin in 3T3-L1 adipocytes and high fat diet induced obesity mice

Yu Su Sin,Sokho Kim,Jungkee Kwon,Jong-Heum Park,Gee-Wook Shin,Seo-Hyun Ahn,Chan Hum Park

doi:10.1186/s13765-020-0489-2

Abstract

Viscum album subsp. Coloratum, also known as Korean mistletoe, is a traditional herb that has more recently been used for the treatment of nervine, hypertensive and cardiovascular diseases. Therefore, this study was undertaken to access the anti-obesity effect of Korean mistletoe-derived polypeptide viscothionin using 3T3-L1 adipocytes in vitro and in vivo mouse experimental model. Viscothionin (up to 5 μM) was used to treat mouse 3T3-L1 pre-adipocytes during adipocyte differentiation. Adipocyte differentiation in 3T3-L1 cells was confirmed by Oil Red O staining. Obesity was induced by a high-fat diet (HFD) in C57BL/6J mice, followed by oral administration of viscothionin (up to 10 mg/kg) for 3 weeks. As a result, viscothionin (5 μM) inhibited differentiation of adipocyte cells and attenuated accumulation of intracellular lipids through activation of 5′-adenosine monophosphate-activated protein kinase (AMPK), by down-regulating phosphorylation in AKT and glycogen synthase kinase 3β (GSK3β). Treatment of viscothionin also decreased the levels of sterol regulatory element binding protein-1 (SREBP-1) and its target gene, fatty acid synthase (FAS). Moreover, viscothionin (10 mg/kg) significantly suppressed body weight and fat content, and improved serum lipid concentration, compared with the standard drug simvastatin (10 mg/kg), a well-known anti-obesity agent. The present study suggests, that viscothionin exerts anti-adipogenic effect through the activation of AMPK and has potential to prevent HFD-induced obesity.

Highlights

Obesity is a complex chronic disorder which is linked to a number of health complications, including diabetes, hypertension, cancer, hyperlipidemia, osteoarthritis, and heart diseases [1]. 3T3-L1 cells are entrenched in vitro model for assessing the differentiation of adipocytes at a number of developmental stages, including, differentiation stages associated with obesity [2]. 3T3-L1 cells have been extensively studied for determining the anti-adipogenic effects of several existing and new therapeutic compounds that have potential to control body weight gain or
Effects of viscothionin on AMPK activation To inquire whether the inhibition of adipocyte differentiation by viscothionin is mediated by AMPK activation, 3T3-L1 cells were treated by 5 μM viscothionin for 8 days
When the 3T3L1 cells were pre-treated with compound C (20 μM), viscothionin-induced phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) were significantly reduced and phosphorylation of AKT and glycogen synthase kinase 3β (GSK3β) was significantly increased (Fig. 1)

Summary

Introduction

3T3-L1 cells are entrenched in vitro model for assessing the differentiation of adipocytes at a number of developmental stages, including, differentiation stages associated with obesity [2]. 5′-Adenosine monophosphate-activated protein kinase (AMPK) is a heterotrimeric protein complex that acts as an energy sensor in homeostasis [4]. AMPK is known to be a significant target of anti-adipogenic and anti-obesity agents. Mistletoe has several pharmacological activities, and can act as a nervine, hypertensive, vasodilator, or relaxant [8,9,10]. No studies have been reported so far on viscothionin whether it possesses anti-adipogenic and anti-obesity effects along with an underlying mechanism for the observed activities. We performed in vivo studies in order to validate the anti-obesity effects of viscothionin using HFD-fed mice as an animal model

Methods

Results

Conclusion