title: A high-throughput screen for inhibitors of the prolyl isomerase, Pin1, identifies a seaweed polyphenol that reduces adipose cell differentiation.
abstract: The peptidyl prolyl cis/trans isomerase Pin1 enhances the uptake of triglycerides and the differentiation of fibroblasts into adipose cells in response to insulin stimulation. Pin1 downregulation could be a potential approach to prevent and treat obesity-related disorders. In order to identify an inhibitor of Pin1 that exhibited minimal cytotoxicity, we established a high-throughput screen for Pin1 inhibitors and used this method to identify an inhibitor from 1,056 crude fractions of two natural product libraries. The candidate, a phlorotannin called 974-B, was isolated from the seaweed, Ecklonia kurome. 974-B inhibited the differentiation of mouse embryonic fibroblasts and 3T3-L1 cells into adipose cells without inducing cytotoxicity. We discovered the Pin1 inhibitor, 974-B, from the seaweed, E. kurome, and showed that it blocks the differentiation of fibroblasts into adipose cells, suggesting that 974-B could be a lead drug candidate for obesity-related disorders.
authors.affiliation: a Molecular Enzymology, Department of Molecular Cell Science, Graduate School of Agricultural Science , Tohoku University , Sendai , Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Mori
authors.forename: Masafumi
authors.initials: M
authors.lastname: Hidaka
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ikuji
authors.forename: Ibuki
authors.initials: I
authors.lastname: Yoshizawa
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Toyohara
authors.forename: Toru
authors.initials: T
authors.lastname: Okuda
authors.forename: Chiyoko
authors.initials: C
authors.lastname: Uchida
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Asano
authors.forename: Mari
authors.initials: M
authors.lastname: Yotsu-Yamashita
authors.forename: Takafumi
authors.initials: T
authors.lastname: Uchida
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D001688:Biological Products / Q000302:isolation & purification / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology; D057166:High-Throughput Screening Assays; D051379:Mice; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors*; D059808:Polyphenols / Q000302:isolation & purification / Q000494:pharmacology*; D012624:Seaweed / Q000737:chemistry*
chemical_list: D001688:Biological Products; D004791:Enzyme Inhibitors; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D059808:Polyphenols; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse
keywords: adipose cell; high-throughput screen; obesity; prolyl isomerase; seaweed polyphenol