title: Coffee extract inhibits adipogenesis in 3T3-L1 preadipocyes by interrupting insulin signaling through the downregulation of IRS1.
abstract: Although epidemiological data have indicated that a strong negative association exists between coffee consumption and the prevalence of obesity-associated diseases, the molecular mechanisms by which coffee intake prevents obesity-associated diseases has not yet been elucidated. In this study, we found that coffee intake significantly suppressed high-fat diet (HFD)-induced metabolic alternations such as increases in body weight and the accumulation of adipose tissue, and up-regulation of glucose, free fatty acid, total cholesterol and insulin levels in the blood. We also found that coffee extract significantly inhibited adipogenesis in 3T3-L1 preadipocytes. In the early phase of adipogenesis, 3T3-L1 cells treated with coffee extract displayed the retardation of cell cycle entry into the G2/M phase called as mitotic clonal expansion (MCE). Coffee extract also inhibited the activation of CCAAT/enhancer-binding protein β (C/EBPβ) by preventing its phosphorylation by ERK. Furthermore, the coffee extract suppressed the adipogenesis-related events such as MCE and C/EBPβ activation through the down-regulation of insulin receptor substrate 1 (IRS1). The stability of the IRS1 protein was markedly decreased by the treatment with coffee extract due to proteasomal degradation. These results have revealed an anti-adipogenic function for coffee intake and identified IRS1 as a novel target for coffee extract in adipogenesis.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Keio University, Minato-ku, Tokyo, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Maki
authors.affiliation: Graduate School of Pharmaceutical Sciences, Keio University, Minato-ku, Tokyo, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Funakoshi-Tago
authors.affiliation: Graduate School of Pharmaceutical Sciences, Keio University, Minato-ku, Tokyo, Japan.
authors.forename: Ryohei
authors.initials: R
authors.lastname: Aoyagi
authors.affiliation: Graduate School of Pharmaceutical Sciences, Keio University, Minato-ku, Tokyo, Japan.
authors.forename: Fumihito
authors.initials: F
authors.lastname: Ueda
authors.affiliation: Graduate School of Pharmaceutical Sciences, Keio University, Minato-ku, Tokyo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kobata
authors.affiliation: Division of Structural Biochemistry, Department of Biochemistry, Jichi Medical University, Shimotsuke-shi, Tochigi-ken, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Tago
authors.affiliation: Graduate School of Pharmaceutical Sciences, Keio University, Minato-ku, Tokyo, Japan.
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Tamura
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D003069:Coffee / Q000737:chemistry* / Q000378:metabolism; D059305:Diet, High-Fat; D015536:Down-Regulation / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D022782:CCAAT-Enhancer-Binding Protein-beta; D003069:Coffee; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D010936:Plant Extracts; D014280:Triglycerides