Abstract
Increased bone marrow adiposity is widely observed in patients with obesity and osteoporosis and reported to have deleterious effects on bone formation. Dracunculin (DCC) is a coumarin isolated from Artemisia spp. but, until now, has not been studied for its bioactive potential except antitrypanosomal activity. In this context, current study has reported the anti-adipogenic effect of DCC in human bone marrow-derived mesenchymal stromal cells (hBM-MSCs). DCC dose-dependently inhibited the lipid accumulation and expression of adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) in hBM-MSCs induced to undergo adipogenesis. To elucidate its action mechanism, the effect of DCC on Wnt/β-catenin and AMPK pathways was examined. Results showed that DCC treatment activated Wnt/β-catenin signaling pathway via AMPK evidenced by increased levels of AMPK phosphorylation and Wnt10b expression after DCC treatment. In addition, DCC treated adipo-induced hBM-MSCs exhibited significantly increased nuclear levels of β-catenin compared with diminished nuclear PPARγ levels. In conclusion, DCC was shown to be able to hinder adipogenesis by activating the β-catenin via AMPK, providing potential utilization of DCC as a nutraceutical against bone marrow adiposity.
Highlights
IntroductionPublished: 7 January 2022Worldwide prevalence of obesity is considered to be one of the main promoters for several common metabolic diseases such as diabetes, cardiovascular problems, and cancer [1]
Initiation of the adipogenesis is strictly regulated by adipogenic transcription factors of which peroxisome proliferator activated receptor gamma (PPARγ) and CCAAT/enhancer binding proteins (C/EBP) are the key factors [3]
The hBM-mesenchymal stromal cells (MSCs) were treated with DCC (Figure 1A) at the concentrations of 1, 5, 10 and 25 μM for 3 days in order to evaluate their cytotoxicity
Summary
Published: 7 January 2022Worldwide prevalence of obesity is considered to be one of the main promoters for several common metabolic diseases such as diabetes, cardiovascular problems, and cancer [1]. Reported links between obesity progression and the prevalence of various other diseases have become a big concern for public health. Obesity is characterized basically with inflammation caused by the hormonal secretions of excessive adipose tissue formation and consequent lipid accumulation in the body. Formation of the adipose tissue and accumulating lipid are results of overstimulated adipogenesis, which is an intricate differentiation process of pre-adipocytes involving several intertwined signaling pathways resulting in differentiation into mature adipocytes [2]. Maturation of adipocytes is characterized with intracellular lipid accumulation and adipocyte-specific gene expressions. Initiation of the adipogenesis is strictly regulated by adipogenic transcription factors of which peroxisome proliferator activated receptor gamma (PPARγ) and CCAAT/enhancer binding proteins (C/EBP) are the key factors [3]. Expression and transcriptional activities of these adipogenic factors, as well as their downstream effector proteins, are mandatory for the progression of adipogenesis
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