Morusin Functions as a Lipogenesis Inhibitor as Well as a Lipolysis Stimulator in Differentiated 3T3-L1 and Primary Adipocytes.

Mi Rim Lee,Ji Won Park,Mi Ju Kang,Kyung Mi Kim,Jun Young Choi,Bo Ram Song,Hye Ryeong Kim,Dae Youn Hwang,Jin Ju Park,Young Whan Choi,Ji Eun Kim

doi:10.3390/molecules23082004

Abstract

Conflicting results for morusin activity during adipogenic differentiation are reported in 3T3-L1 adipocytes and cancer cells. To elucidate the influence of morusin on fat metabolism, their anti-obesity effects and molecular mechanism were investigated in 3T3-L1 cells and primary adipocytes. Morusin at a dose of less than 20 µM does not induce any significant change in the viability of 3T3-L1 adipocytes. The accumulation of intracellular lipid droplets in 3T3-L1 adipocytes stimulated with 0.5 mM 3-isobutyl-1-methylxanthine, 1 µM dexamethasone, 10 µg/mL insulin in DMEM containing 10% FBS (MDI)-significantly reduces in a dose-dependent manner after morusin treatment. The phosphorylation level of members in the MAP kinase signaling pathway under the insulin receptor downstream also decrease significantly in the MDI + morusin-treated group compared to MDI + vehicle-treated group. Also, the expression of adipogenic transcription factors (PPARγ and C/EBPα) and lipogenic proteins (aP2 and FAS) are significantly attenuated by exposure to the compound in MDI-stimulated 3T3-L1 adipocytes. Furthermore, the decrease in the G0/G1 arrest of cell cycle after culturing in MDI medium was dramatically recovered after co-culturing in MDI + 20 µM morusin. Moreover, morusin treatment induces glycerol release in the primary adipocytes of SD rats and enhances lipolytic protein expression (HSL, ATGL, and perilipin) in differentiated 3T3-L1 adipocytes. Overall, the results of the present study provide strong evidence that morusin inhibits adipogenesis by regulating the insulin receptor signaling, cell cycle and adipogenic protein expression as well as stimulating lipolysis by enhancing glycerol release and lipolytic proteins expression.

Highlights

Morusin is a well-known prenylated flavonoid purified from the root bark of Morus austrakis [1,2]and branch bark of Ramulus mori [3]
Our results indicate that morusin prevents lipid accumulation in MDI-stimulated 3T3-L1 cells through the regulation of adipogenic transcription factors, lipogenic proteins during the early stage of adipocytes differentiation, and cell cycle
Our study shows that morusin stimulates lipolysis and inhibits lipogenesis in 3T3-L1 adipocytes

Summary

Introduction

Morusin is a well-known prenylated flavonoid purified from the root bark of Morus austrakis [1,2]and branch bark of Ramulus mori [3]. Morusin dramatically suppresses the growth of different tumor types including breast cancer [5], glioblastoma [6], pancreatic cancer [7], hepatocarcinoma [8], prostate cancer [9], and gastric cancer [10]. It inhibits the inflammatory response by suppressing the COX. One study provided a clue to the possibility that morusin has anti-obesity activity This compound was isolated as one of bioactive compounds from Morus alba var. The treatment of morusin induced the dose-dependent increase of lipid droplets in glioblastoma stem cells (GSCs) and enhanced the levels of adipogenic proteins including

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Conclusion