title: Phenylenediamine derivatives induce GDF-15/MIC-1 and inhibit adipocyte differentiation of mouse 3T3-L1 cells.
abstract: Phenylenediamine derivatives can function as a hydrogen donor and reportedly exert various biological actions including cytoprotective effects against oxidative stress, possibly by acting as an antioxidant. Previous studies showed that feeding of such compounds to mice reduced their body weight, but the precise mechanism remains unknown at present. Here, we found that these compounds inhibited the in vitro differentiation of mouse preadipocytes, 3T3-L1 cells, into adipocytes, suggesting that, at least in part, reduced generation of adipocytes might contribute to the observed weight loss in mice. Next, we performed array analysis and found that the expression of GDF-15/MIC-1, which is a TGFβ superfamily cytokine, and Trib 3, an intracellular downstream effector of the cytokines, was up-regulated by these derivatives. Thus, we identified the compounds as inducers of GDF-15/MIC-1 and suggest that such induction may have led to inhibition of adipocyte differentiation, which could account for the weight-loss effect of these compounds.
authors.affiliation: Department of Welfare Engineering, Faculty of Engineering, Iwate University, Morioka, Iwate, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Yanagitai
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kitagawa
authors.forename: Kyouji
authors.initials: K
authors.lastname: Okawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Koyama
authors.forename: Takumi
authors.initials: T
authors.lastname: Satoh
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D055436:Growth Differentiation Factor 15 / Q000096:biosynthesis*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010655:Phenylenediamines / Q000494:pharmacology*
chemical_list: C526141:Gdf15 protein, mouse; D055436:Growth Differentiation Factor 15; D010655:Phenylenediamines