Identification of KMU-3, a Novel Derivative of Gallic Acid, as an Inhibitor of Adipogenesis

Title
Identification of KMU-3, a Novel Derivative of Gallic Acid, as an Inhibitor of Adipogenesis
Author(s)
이태윤박유경[박유경]홍석봉[홍석봉]최종순[최종순]이진호[이진호]장병철[장병철]
Keywords
ACTIVATED-RECEPTOR-GAMMA; ADIPOCYTE DIFFERENTIATION; 3T3-L1 PREADIPOCYTES; ADIPOSE-TISSUE; C/EBP-ALPHA; PPAR-GAMMA; INSULIN SENSITIVITY; METABOLIC DISEASE; BINDING-PROTEINS; GENE-EXPRESSION
Issue Date
201410
Publisher
PUBLIC LIBRARY SCIENCE
Citation
PLOS ONE, v.9, no.10
Abstract
Differentiation of preadipocyte, also called adipogenesis, leads to the phenotype of mature adipocyte. Excessive adipogenesis, however, is largely linked to the development of obesity. Herein we investigated a library of 53 novel chemicals, generated from a number of polyphenolic natural compounds, on adipogenesis. Strikingly, among the chemicals tested, KMU-3, a derivative of gallic acid, strongly suppressed lipid accumulation during the differentiation of 3T3-L1 preadipocytes into adipocytes. On mechanistic levels, KMU-3 inhibited expressions of CCAAT/enhancer-binding protein-alpha (C/EBP-alpha), peroxisome proliferator-activated receptor-gamma (PPAR-gamma), and fatty acid synthase (FAS) during adipocyte differentiation. Moreover, KMU-3 reduced expressions of adipokines, including retinol binding protein-4 (RBP-4), leptin, and regulated on activation, normal T cell expressed and secreted (RANTES) during adipocyte differentiation. Of further note, KMU-3 rapidly blocked the phosphorylation of signal transducer and activator of transcription-3 (STAT-3) during the early stage of adipogenesis. Importantly, pharmacological inhibition studies revealed that AG490, a JAK-2/STAT-3 inhibitor suppressed adipogenesis and STAT-3 phosphorylation, implying that early blockage of STAT-3 activity is crucial for the KMU-3- mediated anti-adipogenesis. These findings demonstrate firstly that KMU-3 inhibits adipogenesis by down-regulating STAT-3, PPAR-gamma, C/EBP-alpha, and FAS. This work shows that KMU-3 is an inhibitor of adipogenesis and thus may have therapeutic potential against obesity.
URI
http://hdl.handle.net/YU.REPOSITORY/30610http://dx.doi.org/10.1371/journal.pone.0109344
ISSN
1932-6203
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의과대학 > 미생물학교실 > Articles
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