Decursin and Decursinol Angelate Suppress Adipogenesis through Activation of β-catenin Signaling Pathway in Human Visceral Adipose-Derived Stem Cells.

In Sil Park,Untack Cho,Jong Hun Kim,Se Ik Kim,Boyun Kim,Yong Sang Song,Hee Yang,Ki Won Lee,Youngjin Han,Jung Han Yoon Park

doi:10.3390/nu12010013

Abstract

Visceral adiposity is closely associated with metabolic disorders and cardiovascular diseases. Angelica gigas Nakai (AGN) has been reported to possess anti-obesity effects and higher amounts of coumarin compounds are present in AGN. However, the active compounds suppressing adipogenesis in AGN and mechanisms of action have not been investigated in adipose-derived stem cells (ASCs) isolated from visceral adipose tissue (VAT). Among four coumarin compounds of AGN, decursin (D) and decursinol angelate (DA) significantly inhibited adipocyte differentiation from ASCs. D and DA downregulated CCAAT/enhancer binding protein α (C/EBPα), peroxisome proliferator-activated receptor γ (PPARγ), adipocyte fatty acid binding protein (aP2), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) at both mRNA and protein levels. Next, treatment with adipogenic differentiation medium (ADM) on ASCs downregulated β-catenin expression at protein level, while addition of D and DA could restore protein expression and nuclear translocation of β-catenin suppressed by ADM. D and DA treatment on ADM treated ASCs increased inhibitory phosphorylation of Glycogen synthase kinase (GSK)-3β, thereby preventing β-catenin from degradation. Additionally, si-β-catenin transfection significantly upregulated protein expression of C/EBPα and PPARγ, alleviating the anti-adipogenic effect of D and DA on ADM treated ASCs. Overall, D and DA, active compounds from AGN, suppressed adipogenesis through activation of β-catenin signaling pathway in ASCs derived from human VAT, possibly using as natural anti-visceral adiposity agents.

Highlights

Obesity is excessive fat deposition and has a profound impact on quality of life
To evaluate the anti-adipogenic effect of active compounds from Angelica gigas Nakai (AGN), adipose-derived stem cells (ASCs) were differentiated with adipogenic differentiation medium (ADM) in the presence of coumarin compounds (D, decursinol angelate (DA), ND, and dimethyl suberosin (DS)) from AGN at 40 μM for 14 days (Figure 1a)
To further investigate the types of lipid changed by D and DA, triglyceride and cholesterol concentration were quantified after adipogenic induction with ADM and addition of D and DA on ADM treated ASCs

Summary

Introduction

Visceral obesity characterized by high visceral adipose tissue (VAT) distribution in intra-abdominal, associated with a high risk of metabolic disorders including type 2 diabetes, hypertension, and atherosclerosis [1,2]. Obesity is induced by adipogenesis impairments of adipocytes in adipose tissue increasing lipid accumulation. Adipogenesis is a complex process which includes increase of adipocyte differentiation from adipose-derived stem cells (ASCs) and intracellular lipid accumulation [3]. We showed differential gene expression pattern of ASCs between human VAT and subcutaneous adipose tissue (SAT). VAT-derived ASCs showed higher expression of gene clusters involved in lipid biosynthesis than SAT-derived ASCs, suggesting that VAT-derived ASCs may have higher adipogenic potential [4]. Inhibition of adipogenesis of VAT-derived ASCs could be an ideal therapeutic strategy for treating visceral obesity

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