Abstract

Regulating the adipogenic differentiation mechanism is a valid and promising mechanism to battle obesity. Natural products, especially phytochemicals as nutraceuticals, are important lead molecules with significant activities against obesity. Loliolide is a monoterpenoid hydroxyl lactone found in many dietary plants. The effect of loliolide on adipogenic differentiation is yet to be determined. Therefore, the present study aimed to evaluate its anti-adipogenic potential using human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) and assess its mechanism of action. Adipo-induced hBM-MSCs were treated with or without loliolide and their adipogenic characteristics were examined. Loliolide treatment decreased the lipid accumulation and expression of adipogenic transcription factors, PPARγ, C/EBPα, and SREBP1c. Adipo-induced hBM-MSCs also displayed increased AMPK phosphorylation and suppressed MAPK activation following loliolide treatment according to immunoblotting results. Importantly, loliolide could stimulate Wnt10b expression and active β-catenin translocation to exert PPARγ-linked adipogenesis suppression. In conclusion, loliolide was suggested to be a potential anti-adipogenic agent which may be utilized as a lead compound for obesity treatment or prevention.

Highlights

  • Obesity is a serious medical concern in today’s world and characterized by excess fat accumulation which is an aesthetic problem and an underlying cause of several diseases such as cardiovascular diseases, different types of cancer, organ failures, and diabetes [1,2]

  • Prior to assessing its anti-adipogenic properties, the cytotoxicity of loliolide was tested on hBM-MSCs via MTT assay. the results show that, with up to 10 μM loliolide treatment, there was no loss of viability (Figure 1B)

  • Adipogenesis of hBM-MSCs in response to loliolide treatment following adipogenic differentiation medium administration was evaluated at Day 10 of differentiation

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Summary

Introduction

Obesity is a serious medical concern in today’s world and characterized by excess fat accumulation which is an aesthetic problem and an underlying cause of several diseases such as cardiovascular diseases, different types of cancer, organ failures, and diabetes [1,2]. Excess accumulation of body fat occurs through elevated levels of adipose tissue formation, which is a result of adipogenic differentiation of adipogenic progenitor stem cells. The close and complex regulatory relations between white and brown adipose tissues, which are the most abundant distinct adipose tissues in the human body, are considered to be the reason behind the obesity onset and progression [4]. The differentiation capabilities and roles they take in various mechanisms in homeostasis make human mesenchymal stem cells promising targets for regenerative medicine and have been utilized in several studies against diabetes, cardiovascular diseases, and osteoarthritis [5]

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