title: Hirsutenone Directly Targets PI3K and ERK to Inhibit Adipogenesis in 3T3-L1 Preadipocytes.
abstract: Adipogenesis is a key driver of the expansion of adipose tissue mass that causes obesity. Hirsutenone (HST) is an active botanical diarylheptanoid present in Alnus species. In this study, we evaluated the effects of HST on adipogenesis, its mechanisms of action and the molecular targets involved. Using Oil Red O staining, we observed that HST dose-dependently suppresses lipid accumulation during adipogenesis in 3T3-L1 preadipocytes, concomitant with a decrease in peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα) and fatty acid synthase (FAS) protein expression. This inhibitory effect was largely limited to the early stage of adipogenesis, which includes mitotic clonal expansion (MCE), as evidenced by delayed cell cycle entry of preadipocytes from G1 to S phase. Furthermore, the regulation of MCE was accompanied by suppression of phosphatidylinositol 3-kinase (PI3K) and extracellular-regulated kinase (ERK) activity. HST was also shown to bind directly to PI3K and ERK1 in a non-ATP competitive manner. Our results suggest that HST attenuates adipogenesis by directly targeting PI3K and ERK during MCE in 3T3-L1 preadipocytes, underscoring the potential therapeutic application of HST in preventing obesity.
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Lai Yee
authors.initials: LY
authors.lastname: Cheong
authors.affiliation: Interdisciplinary Program in Agricultural Biotechnology Major, College of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sujin
authors.initials: S
authors.lastname: Suk
authors.affiliation: Chemical Biology Research Center and World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.
authors.forename: N R
authors.initials: NR
authors.lastname: Thimmegowda
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.|Division of Metabolism and Functionality Research, Korea Food Research Institute, Seongnam, Republic of Korea.
authors.forename: Min-Yu
authors.initials: MY
authors.lastname: Chung
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hee
authors.initials: H
authors.lastname: Yang
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sang Gwon
authors.initials: SG
authors.lastname: Seo
authors.affiliation: Chemical Biology Research Center and World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.
authors.forename: B
authors.initials: B
authors.lastname: Shwetha
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.|Research Institute of Bio Food Industry, Institute of Green Bio Science and Technology, Seoul National University, Pyeongchang, Republic of Korea.
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Kwon
authors.affiliation: Chemical Biology Research Center and World Class Institute, Korea Research Institute of Bioscience and Biotechnology, Ochang, Republic of Korea.
authors.forename: Bo Yeon
authors.initials: BY
authors.lastname: Kim
authors.affiliation: WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul, Republic of Korea.|Interdisciplinary Program in Agricultural Biotechnology Major, College of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.|Research Institute of Bio Food Industry, Institute of Green Bio Science and Technology, Seoul National University, Pyeongchang, Republic of Korea.|Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Republic of Korea.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D002396:Catechols / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D036381:Diarylheptanoids / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*
chemical_list: D002396:Catechols; D036381:Diarylheptanoids; C508777:hirsutenone; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases
keywords: ADIPOGENESIS; ERK; HIRSUTENONE; MITOTIC CLONAL EXPANSION; PI3K