Arctigenin Inhibits Adipogenesis by Inducing AMPK Activation and Reduces Weight Gain in High‐Fat Diet‐Induced Obese Mice

Han, Yohan; Kee, Ji‐Ye; Park, Jin Bong; Kim, Hye-Lin; Jeong, Mi-Young; Kim, Daeseung; Jeon, Yong-Deok; Jung, Yoon Suk; Youn, Dong‐Hyun; Kang, JongWook; So, Hong-Seob; Park, Raekil; Lee, Jong‐Hyun; Shin, Soyoung; Kim, Sujin; Um, Jae‐Young; Hong, Seung‐Heon

doi:10.1002/jcb.25509

Cited by 37 publications

(35 citation statements)

References 50 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: 67%

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: 67%

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

et al. 2019

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“…Former study demonstrated that the phosphorylation of AMPK (p-AMPK) could inhibit the differentiation of pre-adipocytes [16, 22]. In this study, we detected the level of p-AMPK in cells treated with various concentrations of PAQG, and the results showed that p-AMPK in the differentiation process of 3T3-L1 was upregulated dose-dependently by PAQG (Fig.…”

Section: Resultsmentioning

confidence: 61%

“…To further illustrating the effect of PAQG on the activation of AMPK, we exposed L6 cells with AICAR and compound C, specific activator and inhibitor of AMPK, respectively [16]. Compared to the vehicle treatment, compound C markedly reduced the activation of AMPK.…”

Section: Resultsmentioning

confidence: 99%

“…[15]. Previous studies showed that AMPK activation could inhibit the differentiation of pre-adipocytes, induce the reduction of lipid accumulation and acceleration of lipolysis [14, 16, 17], which are pivotal signaling pathway for the treatment of obesity. In this study, PAQG inhibited the differentiation of 3T3-L1 pre-adipocytes and reduced the lipid accumulation in adipocytes, it may exert the effects via promoting AMPK pathway, suggesting a novel and potent candidate in drug development.…”

Section: Introductionmentioning

confidence: 99%

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Pyrocincholic acid 3β-O-β-d-quinovopyranosyl-28-O-β-d-glucopyranoside suppresses adipogenesis and regulates lipid metabolism in 3T3-L1 adipocytes

et al. 2017

Nat. Prod. Bioprospect.

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Obesity is crucially involved in many metabolic diseases, such as type 2 diabetes, cardiovascular disease and cancer. Regulating the number or size of adipocytes has been suggested to be a potential treatment for obesity. In this study, we investigated the effect of pyrocincholic acid 3β-O-β-d-quinovopyranosyl-28-O-β-d-glucopyranoside (PAQG), a 27-nor-oleanolic acid saponin extracted from Metadina trichotoma, on adipogenesis and lipid metabolism in 3T3-L1 adipocytes. The 3T3-L1 pre-adipocytes were incubated with vehicle or PAQG for 6 days in differentiation process. PAQG significantly reduced the adipogenesis, adiponectin secretion and the expression level of key transcription factors related to adipogenesis, such as PPARγ, C/EBPβ, C/EBPα, and FABP4. Moreover, PAQG increased the levels of FFA and glycerol in medium and reduced TG level in mature adipocytes. Interestingly, PAQG not only promoted the activation of AMPK and genes involved in fatty oxidation including PDK4 and CPT1a, but also inhibited those genes involved in fatty acid biosynthesis, such as SREBP1c, FAS, ACCα and SCD1. In conclusion, PAQG inhibits the differentiation and regulates lipid metabolism of 3T3-L1 cells via AMPK pathway, suggesting that PAQG may be a novel and promising natural product for the treatment of obesity and hyperlipidemia.Graphical Abstract Electronic supplementary materialThe online version of this article (doi:10.1007/s13659-017-0127-9) contains supplementary material, which is available to authorized users.

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“…Besides inflammation pathways, the AMP‐activated protein kinase (AMPK) pathway has also been reported to be the target of ARC, where ARC was shown to ameliorate experimental autoimmune encephalomyelitis through activating AMPK (Li et al, ). Han et al also reported that ARC inhibited adipogenesis and reduced weight gain in high‐fat diet‐induced obese mice by inducing AMPK (Han et al, ). The above evidences consistently suggest AMPK pathway as one of the potential underlying molecular mechanisms to explain ARC functions observed both in this study and others, which certainly warrants further research efforts.…”

Section: Discussionmentioning

confidence: 99%

Arctigenin protects against neuronal hearing loss by promoting neural stem cell survival and differentiation

Huang

Chen

Ding

et al. 2017

Genesis

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Neuronal hearing loss has become a prevalent health problem. This study focused on the function of arctigenin (ARC) in promoting survival and neuronal differentiation of mouse cochlear neural stem cells (NSCs), and its protection against gentamicin (GMC) induced neuronal hearing loss. Mouse cochlea was used to isolate NSCs, which were subsequently cultured in vitro. The effects of ARC on NSC survival, neurosphere formation, differentiation of NSCs, neurite outgrowth, and neural excitability in neuronal network in vitro were examined. Mechanotransduction ability demonstrated by intact cochlea, auditory brainstem response (ABR), and distortion product optoacoustic emissions (DPOAE) amplitude in mice were measured to evaluate effects of ARC on GMC-induced neuronal hearing loss. ARC increased survival, neurosphere formation, neuron differentiation of NSCs in mouse cochlear in vitro. ARC also promoted the outgrowth of neurites, as well as neural excitability of the NSC-differentiated neuron culture. Additionally, ARC rescued mechanotransduction capacity, restored the threshold shifts of ABR and DPOAE in our GMC ototoxicity murine model. This study supports the potential therapeutic role of ARC in promoting both NSCs proliferation and differentiation in vitro to functional neurons, thus supporting its protective function in the therapeutic treatment of neuropathic hearing loss in vivo.

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Arctigenin Inhibits Adipogenesis by Inducing AMPK Activation and Reduces Weight Gain in High‐Fat Diet‐Induced Obese Mice

Cited by 37 publications

References 50 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

Pyrocincholic acid 3β-O-β-d-quinovopyranosyl-28-O-β-d-glucopyranoside suppresses adipogenesis and regulates lipid metabolism in 3T3-L1 adipocytes

Arctigenin protects against neuronal hearing loss by promoting neural stem cell survival and differentiation

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