title: Secreted nucleobindin-2 inhibits 3T3-L1 adipocyte differentiation.
abstract: Nucleobindin-2 is a 420 amino acid EF-hand Ca²⁺ binding protein that can be further processed to generate an 82 amino terminal peptide termed Nesfatin-1. To examine the function of secreted Nucleobindin-2 in adipocyte differentiation, cultured 3T3-L1 cells were incubated with either 0 or 100 nM of GST, GST-Nucleobindin-2, prior to and during the initiation of adipocyte differentiation. Nucleobindin-2 treatment decreased neutral lipid accumulation (Oil-Red O staining) and expression of several marker genes for adipocyte differentiation (PPARγ, aP2, and adipsin). When Nucleobindin- 2 was constitutively secreted into cultured medium, cAMP content and insulin stimulated CREB phosphorylation were significantly reduced. On the other hand, intracellularly overexpressed Nucleobindin-2 failed to affect cAMP content and CREB phosphorylation. Taken together, these data indicate that secreted Nucleobindin-2 is a suppressor of adipocyte differentiation through inhibition of cAMP production and insulin signal.
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39- 15 Showa-machi, Maebashi, Gunma 371-8511, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tagaya
authors.forename: Aya
authors.initials: A
authors.lastname: Osaki
authors.forename: Atsuko
authors.initials: A
authors.lastname: Miura
authors.forename: Shuichi
authors.initials: S
authors.lastname: Okada
authors.forename: Kihachi
authors.initials: K
authors.lastname: Ohshima
authors.forename: Koshi
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Masanobu
authors.initials: M
authors.lastname: Yamada
authors.forename: Tetsurou
authors.initials: T
authors.lastname: Satoh
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shimizu
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis; D000818:Animals; D002135:Calcium-Binding Proteins / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D000080866:Nucleobindins; D051381:Rats
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D007328:Insulin; C000630650:NUCB2 protein, human; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D000242:Cyclic AMP