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

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.

The Beneficial Effects of Morusin, an Isoprene Flavonoid Isolated from the Root Bark of Morus

“…Morusin has also been highlighted as a potent de novo lipogenesis inhibitor as well as a lipolysis stimulator [ 64 ]. The study was performed in 3T3-L1 and primary adipocytes in which morusin treatment leads to reduced lipid build-up and increased lipid breakdown.…”

“…Although no studies have yet tested the effects of morusin on the pathogenesis of type II diabetes using relevant in vivo models (e.g., ob/ob , db/db mouse or HFD-fed mice) , morusin may also exert anti-diabetes effects in this context, considering that morusin potentially regulates systemic ROS levels, lipogenesis, lipolysis, C/EBPβ and PPARγ signaling, arachidonic acid metabolism and ER-resident proteins implicated in ER stress [ 16 , 59 , 64 ], all of which have been frequently implicated in type II diabetes as well as type I diabetes [ 42 , 63 , 86 , 87 ].…”

“…(3) Morusin may directly target the MAPK pathway in renal carcinoma in vitro, although this should be further validated considering the intimate crosstalk between the NF-κB and MAPK pathway [ 54 ]. (4) C/EBPβ- and PPARγ-mediated lipoapoptosis may be therapeutically relevant targets of morusin in breast cancers, proposed in a study using multiple breast cancer cell lines and a xenograft model of breast cancers [ 64 ]. This may be of great importance considering that the capacity of mitochondrial fatty acid oxidation and fatty acid availability associated with host metabolism have recently emerged as key factors contributing to the pathogenesis of breast cancers [ 91 , 92 ].…”

The Pro-Health Benefits of Morusin Administration—An Update Review

“…These results, however, did not explain the mechanism of morusin function in lipid metabolism. In order to elucidate the effect of morusin on fat metabolism, a study with the use of 3T3-L1 and primary adipocytes was performed [ 73 ]. It was proved that morusin inhibits adipogenesis by regulating the insulin receptor signaling, cell cycle and expression of adipogenic protein.…”

Mori Cortex Radicis extract inhibits human norovirus surrogate in simulated digestive conditions

“…Morusin and kuwanon G are the biological marker compounds in MCR (Eom et al, 2017 ; Kim et al, 2015 ). Morusin, an isoprenylated flavone, reportedly possesses multifunctional bioactivities, including anti-allergic, anti-cancer, and lipogenesis inhibitory activities (Choi et al, 2020 ; Jin et al, 2019 ; Lee et al, 2018 ). Morusin demonstrates antimicrobial activity on Staphylococcus aureus (Pang et al, 2019 ).…”