Inhibitory effect of sinigrin on adipocyte differentiation in 3T3-L1 cells: Involvement of AMPK and MAPK pathways

Lee, Hee-Weon; Rhee, Dong‐Kwon; Kim, Byung-Oh; Pyo, Suhkneung

doi:10.1016/j.biopha.2018.03.124

Cited by 46 publications

(41 citation statements)

References 32 publications

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“…47,48 Consistent with these reports, we showed that ezetimibe can attenuate lipogenesis target genes by inhibiting mTORC1 pathway. 38,49,50 Our results also showed that ezetimibe could reduce lipogenesis-associated genes dependently on the AMPK-mTORC1 pathway. 38,49,50 Our results also showed that ezetimibe could reduce lipogenesis-associated genes dependently on the AMPK-mTORC1 pathway.…”

Section: Discussionsupporting

confidence: 68%

“…8 Furthermore, recent studies showed that the induction of the cell cycle arrest at the G0/G1 phase suppresses MCE, resulting in the inhibition of adipogenesis. [37][38][39] Here, we also found that ezetimibe could arrest the cell cycle at the G0/G1 phase, which induced the AMPK-dependent inhibition of cell proliferation dependently on AMPK in the early stage of adipogenesis. [37][38][39] Here, we also found that ezetimibe could arrest the cell cycle at the G0/G1 phase, which induced the AMPK-dependent inhibition of cell proliferation dependently on AMPK in the early stage of adipogenesis.…”

Section: Discussionsupporting

confidence: 59%

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Ezetimibe ameliorates lipid accumulation during adipogenesis by regulating the AMPK–mTORC1 pathway

et al. 2019

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Adipogenesis, a critical process that converts adipocyte precursors into adipocytes, is considered a potential therapeutic target for the treatment of obesity. Ezetimibe, a drug approved by the United States Food and Drug Administration, is used for the treatment of hypercholesterolemia. Recently, it was reported to ameliorate high fat diet‐induced dyslipidemia in mice and reduce lipid accumulation in hepatocytes through the activation of AMPK. However, the anti‐adipogenic effects of ezetimibe and the underlying molecular mechanism have not yet been elucidated. Here, we found that ezetimibe reduced lipid accumulation via activating AMPK during the early phase of adipogenesis. We also observed that ezetimibe inhibited peroxisome proliferator‐activated receptor γ, which is a major transcription factor of adipogenesis. Furthermore, ezetimibe‐mediated AMPK activation reduced lipid accumulation by inhibiting mTORC1 signaling, leading to the downregulation of lipogenesis‐related genes. Mitotic clonal expansion, required for adipogenesis, accelerates cell cycle progression and cell proliferation. We additionally observed that ezetimibe prevented the progression of mitotic clonal expansion by arresting the cell cycle at the G0/G1 phase, which was followed by the inhibition of cell proliferation. Collectively, ezetimibe‐mediated inhibition of adipogenesis is dependent on the AMPK–mTORC1 pathway. Thus, we suggest that ezetimibe might be a promising drug for the treatment of obesity.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionsupporting

confidence: 59%

Ezetimibe ameliorates lipid accumulation during adipogenesis by regulating the AMPK–mTORC1 pathway

et al. 2019

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“…Several anti-obesity compounds contribute to the regulation of cell cycle progression in MDI-stimulated 3T3-L1 cells. The decrease of G0/G1 arrested population in MDI-stimulated cells recovered after treatment with dioscin [ 27 ], ramalin [ 20 ], and sinigrin [ 28 ]. In addition, cell cycle progression is mediated by MAPK signaling pathway during adipogenesis [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…Among the essential properties of an anti-obesity drug, lipogenic activity and lipolytic activity are considered very important. However, recent studies have focused on the lipogenic activity of single compounds isolated from medicinal plants and have not evaluated their lipolytic activity [ 7 , 22 , 27 , 28 ]. Only a few studies have reported the lipolytic activity of single compounds from herbal plants.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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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.

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“…2-propenylglucosinolate (sinigrin, SG) is a natural aliphatic glucoside that is found in the seeds of Brassica plants including many cough relieving and antiasthmatic traditional Chinese medicines (TCMs) such as Descurainiae Semen (Baek et al, 2018), Raphani Semen (Sham et al, 2013, and Sinapis Semen (Liu et al, 2003). As a major component of these TCMs, many pharmacological activities for SG have been identified such as anticancer (Jie et al, 2014), antiinflammatory (Lee et al, 2017;Lee et al, 2018), wound healing (Mazumder et al, 2016), and antiadipogenic (Lee et al, 2018) properties. However, the antiasthmatic effects of SG remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Sinigrin Enhanced Antiasthmatic Effects of Beta Adrenergic Receptors Agonists by Regulating cAMP-Mediated Pathways

Chu

Liu

et al. 2020

Front. Pharmacol.

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Millions of patients suffer from asthma worldwide. However, the first-line drugs used to treat asthma, namely, the beta-adrenergic receptors agonists (b-agonists), are not recommended for use as monotherapy because of their severe dose-related side effects. This limitation has prompted the search for new therapies, which can be used in conjunction with b-agonists so that lower doses can be administered. Sinigrin is a major compound found in many antiasthmatic medicinal plants. In this study, we explored the antiasthmatic activity of sinigrin when used in combination with b-agonists and its underlying mechanism. Sinigrin enhanced the asthma-relieving effects of isoproterenol and reduced the effective isoproterenol dose in an acute-asthma model in guinea pigs. Mechanistically, sinigrin enhanced the cAMP levels induced by b-agonists by inhibiting PDE4. The resulting increase in cAMP levels stimulated the activity of the downstream effector protein kinase A, which would be expected to ultimately induce the relaxation of airway smooth muscle. In conclusion, sinigrin enhances the asthma-relieving effects of bagonists by regulating the cAMP signaling pathway and represents a potential add-on drug to b-agonists for the treatment of asthma.

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Inhibitory effect of sinigrin on adipocyte differentiation in 3T3-L1 cells: Involvement of AMPK and MAPK pathways

Cited by 46 publications

References 32 publications

Ezetimibe ameliorates lipid accumulation during adipogenesis by regulating the AMPK–mTORC1 pathway

Ezetimibe ameliorates lipid accumulation during adipogenesis by regulating the AMPK–mTORC1 pathway

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

Sinigrin Enhanced Antiasthmatic Effects of Beta Adrenergic Receptors Agonists by Regulating cAMP-Mediated Pathways

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