Inula britannica Inhibits Adipogenesis of 3T3-L1 Preadipocytes via Modulation of Mitotic Clonal Expansion Involving ERK 1/2 and Akt Signaling Pathways

Hyung-Seok Yu,Hyun-Dong Paik,Won-Young Bae,Won-Ju Kim,Na-Kyoung Lee

doi:10.3390/nu12103037

Abstract

The flower of Inula britannica contains various phenolic compounds with prophylactic properties. This study aimed to determine the anti-adipogenic effect of an I. britannica flower aqueous extract (IAE) and its underlying mechanisms in the 3T3-L1 preadipocytes and to identify the phenolic compounds in the extract. Treatment with IAE inhibited the adipogenesis of 3T3-L1 preadipocytes by showing a dose-dependently suppressed intracellular lipid accumulation and significantly mitigated expression levels of lipogenesis- and adipogenesis-associated biomarkers including transcription factors. IAE exerted an anti-adipogenic effect through the modulation of the early phases of adipogenesis including mitotic clonal expansion (MCE). Treatment with IAE inhibited MCE by arresting the cell cycle at the G0/G1 phase and suppressing the activation of MCE-related transcription factors. Furthermore, IAE inhibited adipogenesis by regulating the extracellular signal-regulated kinase 1/2 and Akt signaling pathways. Protocatechuic acid, chlorogenic acid, kaempferol-3-O-glucoside, and 6-methoxyluteolin, which are reported to exhibit anti-adipogenic properties, were detected in IAE. Therefore, modulation of early phases of adipogenesis, especially MCE, is a key mechanism underlying the anti-adipogenic activity of IAE. In summary, the anti-obesity effects of IAE can be attributed to its phenolic compounds, and hence, IAE can be used for the development of anti-obesity products.

Highlights

Adipose tissue is crucially involved in various biological functions such as energy homeostasis, hormonal regulation, and metabolism by secreting the hormones, growth factors, and adipokines as well as function as an energy reservoir [1,2]
These results indicated that Inula britannica flower aqueous extract (IAE) inhibits adipogenesis phosphorylation of CCAAT/enhancer-binding proteins (C/EBPs)-α and modulation of uptake3T3-L1
These results indicated that IAE inhibits adipogenesis and subsequent intracellular lipid accumulation in differentiated 3T3-L1 cells through regulating the Akt/glycogen synthase kinase (GSK)-3β signaling pathways

Summary

Introduction

Adipose tissue is crucially involved in various biological functions such as energy homeostasis, hormonal regulation, and metabolism by secreting the hormones, growth factors, and adipokines as well as function as an energy reservoir [1,2]. A chronic imbalance between the intake and consumption of energy promotes the aberrant growth of adipose tissue accompanying hyperplasia and/or hypertrophy of the adipocytes, resulting in the development of obesity [3]. Obesity is a growing socioeconomic health concern as it is pathologically associated with development of the various degenerative disease such as type-2 diabetes mellitus, hypertension, dyslipidemia, and cardiovascular disease [4]. Nutrients 2020, 12, 3037 extra medical expenditure for obesity and obesity-associated disorders as a socioeconomic burden [6].

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