Clinical application of Nesfatin-1 to obesity from the point of the suppression of adipogenesis.

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Nucleobindin-2 is a 396 amino acid EF-hand Ca^<2+> binding protein that can be further processed to generate an 82 amino terminal peptide termed Nesfatin-1. To examine the function of Nucleobindin-2 in adipocyte differentiation, culutred 3T3-L1 adipogenesis were incubated with various concentrations of GST, GST-Nucleobindin-2, GST-DNesfatin-1 or GST-Nesfatin-1 prior to and during the initiation of adipocyte differentiation. Nucleobindin-2 treatment at physiological concentrations decreased neutral lipid accumulation (Oil-Red O staining) and expression of several marker genes for adipocyte differentiation (PPAR・, aP2, and adipsin). In contrast, deletion of the Nesfatin-1 domain in Nucleobindin-2 (DNesfatin-1) had no significant effect on 3T3-L1 adipocyte differentiation. Although Nesfatin-1 treatment alone also reduced 3T3-L1 adipocyte differentiation and expression of marker genes, this required super physiologic concentrations. Moreover, 3T3-L1 cells stably over expresseing Nuclobindin-2 displayed a significant reduction of adipocyte differentiation. In contrast, reduced expression of Nucleobindin-2 by shRNA resulted in a marked increase of adipocyte differentiation. Taken together, these data indicate that Nucleobindin-2 is secreted from preadipocytes and functions as a suppressor of adipocyte differentiation.