TY - JOUR
T1 - A Novel Bongkrekic Acid Analog-Mediated Modulation of the Size of Lipid Droplets
T2 - Evidence for the Appearance of Smaller Adipocytes
AU - Okazaki, Hiroyuki
AU - Takeda, Shuso
AU - Ishii, Hiroyuki
AU - Takemoto, Yukimi
AU - Fujita, Satoshi
AU - Suyama, Masaki
AU - Matsumoto, Kenji
AU - Shindo, Mitsuru
AU - Aramaki, Hironori
N1 - Funding Information:
This work was performed under the Research Program of “Dynamic Alliance for Open Innovation Bridging Human, Environment and Materials” in “Network Joint Research Center for Materials and Devices” [Research Nos. 20163071 and 20173065 (to H.A.)]. This study was also supported, in part, by JSPS KAKENHI Grant Numbers JP26293004 and JP16H01157 (to M.S.).
Publisher Copyright:
© 2017 The Pharmaceutical Society of Japan
PY - 2017
Y1 - 2017
N2 - Thiazolidinediones (TZDs) are known as peroxisome proliferator-activated receptor γ (PPARγ) activators, and are used in the treatment of diabetes. Although the usefulness of TZDs has been demonstrated, some of their side effects are becoming an obstacle to their clinical applicability; edema is known to be evoked by the “structural characteristics” of TZD, but not by the PPAR? activation. Thus, novel therapeutic modalities (i.e., non-TZD-type PPAR? activators) having different structures to those of TZDs are desired. We previously identified bongkrekic acid (BKA) as a PPAR? activator using the human breast cancer MCF-7 cell line as a model system. In the present study, we newly synthesized BKA analogs and examined the usefulness of BKA and its analogs as PPAR? activators in differentiated adipocyte cells. Among the chemicals investigated, one of the BKA analogs (BKA-#2) strongly stimulated PPAR? and the differentiation of 3T3-L1 cells similar to pioglitazone, a positive control. Furthermore, BKA-#2 reduced the size of lipid droplets in the mature adipocyte cells. The possible modulation mechanism by BKA-#2 is discussed.
AB - Thiazolidinediones (TZDs) are known as peroxisome proliferator-activated receptor γ (PPARγ) activators, and are used in the treatment of diabetes. Although the usefulness of TZDs has been demonstrated, some of their side effects are becoming an obstacle to their clinical applicability; edema is known to be evoked by the “structural characteristics” of TZD, but not by the PPAR? activation. Thus, novel therapeutic modalities (i.e., non-TZD-type PPAR? activators) having different structures to those of TZDs are desired. We previously identified bongkrekic acid (BKA) as a PPAR? activator using the human breast cancer MCF-7 cell line as a model system. In the present study, we newly synthesized BKA analogs and examined the usefulness of BKA and its analogs as PPAR? activators in differentiated adipocyte cells. Among the chemicals investigated, one of the BKA analogs (BKA-#2) strongly stimulated PPAR? and the differentiation of 3T3-L1 cells similar to pioglitazone, a positive control. Furthermore, BKA-#2 reduced the size of lipid droplets in the mature adipocyte cells. The possible modulation mechanism by BKA-#2 is discussed.
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U2 - 10.1248/bpb.b16-00915
DO - 10.1248/bpb.b16-00915
M3 - Article
C2 - 28769000
AN - SCOPUS:85026754638
SN - 0918-6158
VL - 40
SP - 1192
EP - 1198
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
IS - 8
ER -
