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Open AccessArticle

A Potential Nutraceutical Candidate Lactucin Inhibits Adipogenesis through Downregulation of JAK2/STAT3 Signaling Pathway-Mediated Mitotic Clonal Expansion

Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China
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Author to whom correspondence should be addressed.
These authors contributed equally to the article as first authors.
Cells 2020, 9(2), 331; https://doi.org/10.3390/cells9020331
Received: 24 December 2019 / Revised: 15 January 2020 / Accepted: 19 January 2020 / Published: 31 January 2020
(This article belongs to the Special Issue Adipocytes and Metabolic Health)
The prevalence of obesity has increased dramatically worldwide in the past ~50 years. Searching for safe and effective anti-obesity strategies are urgently needed. Lactucin, a plant-derived natural small molecule, is known for anti-malaria and anti-hyperalgesia. The study is to investigate whether lactucin plays a key role in adipogenesis. To this end, in vivo male C57BL/6 mice fed a high-fat diet (HFD) were treated with 20 mg/kg/day of lactucin or vehicle by gavage for seven weeks. Compared with vehicle-treated controls, Lactucin-treated mice showed lower body mass and mass of adipose tissue. Consistently, in vitro 3T3-L1 cells were treated with 20 μM of lactucin. Compared to controls, lactucin-treated cells showed significantly less lipid accumulation during adipocyte differentiation and lower levels of lipid synthesis markers. Mechanistically, we showed the anti-adipogenic property of lactucin was largely limited to the early stage of adipogenesis. Lactucin-treated cells fail to undergo mitotic clonal expansion (MCE). Further studies demonstrate that lactucin-induced MCE arrests might result from reduced phosphorylation of JAK2 and STAT3. We then asked whether activation of JAK2/STAT3 would restore the inhibitory effect of lactucin on adipogenesis with pharmacological STAT3 activator colivelin. Our results revealed similar levels of lipid accumulation between lactucin-treated cells and controls in the presence of colivelin, indicating that inactivation of STAT3 is the limiting factor for the anti-adipogenesis of lactucin in these cells. Together, our results provide the indication that lactucin exerts an anti-adipogenesis effect, which may open new therapeutic options for obesity. View Full-Text
Keywords: lactucin; adipogenesis; JAK2/STAT3; mitotic clonal expansion (MCE); adipocyte; obesity lactucin; adipogenesis; JAK2/STAT3; mitotic clonal expansion (MCE); adipocyte; obesity
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Wang, X.; Liu, M.; Cai, G.H.; Chen, Y.; Shi, X.C.; Zhang, C.C.; Xia, B.; Xie, B.C.; Liu, H.; Zhang, R.X.; Lu, J.F.; Zhu, M.Q.; Yang, S.Z.; Chu, X.Y.; Zhang, D.Y.; Wang, Y.L.; Wu, J.W. A Potential Nutraceutical Candidate Lactucin Inhibits Adipogenesis through Downregulation of JAK2/STAT3 Signaling Pathway-Mediated Mitotic Clonal Expansion. Cells 2020, 9, 331.

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