Placental extract suppresses differentiation of 3T3-L1 preadipocytes to mature adipocytes via accelerated activation of p38 MAPK during the early phase of adipogenesis

Nutrition & Metabolism

Yoshihiko Chiba¹  Junzo Kamei²  Yusuke Ando²  Hazuki Fukunaga³  Fumiaki Sato³  Yusuke Iwasaki⁴  Masahiko Tebakari⁵  Yuki Daigo⁵  Junichi Kawashima⁶ 

[1] 0000 0004 1770 141X, grid.412239.f, Department of Physiology and Molecular Sciences, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, 142-8501, Tokyo, Japan;0000 0004 1770 141X, grid.412239.f, Global Research Center for Innovative Life Science, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, 142-8501, Tokyo, Japan;0000 0004 1770 141X, grid.412239.f, Laboratory of Analytical Pathophysiology, Division of Pharmacy Professional Development and Research, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, 142-8501, Tokyo, Japan;0000 0004 1770 141X, grid.412239.f, Laboratory of Biopharmaceutics Analytical Science, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, 142-8501, Tokyo, Japan;Pharmaceutical Research Laboratory, Snowden Co., Ltd., 793 Futatsumiya, Nishi-ku, 331-0065, Saitama, Japan;Pharmaceutical Research Laboratory, Snowden Co., Ltd., 793 Futatsumiya, Nishi-ku, 331-0065, Saitama, Japan;R&D Merchandising Division, Snowden Co., Ltd., 3-7-16 Iwamoto-cho, Chiyoda-ku, 101-0032, Tokyo, Japan;

关键词: Placental extract;    3T3-L1;    Adipogenesis;    Obesity;    p38 MAPK;    PPARγ;   

DOI  :  10.1186/s12986-019-0361-8

来源: publisher

【 摘 要 】

BackgroundAdipogenesis, the process of preadipocyte differentiation to mature adipocytes accompanied by accumulation of intracytoplasmic lipid droplets, is regulated by various genetic and environmental factors, and closely associated with the development of obesity. Numerous recent studies suggest that some bioactive peptides and proteins derived from animals, and chemical compounds isolated from plants may be useful for prevention and treatment of obesity and obesity-related chronic diseases. In the present study, we examined the broad spectrum of effects of placental extract, with a focus on the influence of placental extract on adipogenesis.MethodWe cultured 3T3-L1 cells, which are widely used as a model of white preadipocytes, under differentiation conditions in the presence of porcine placental extract (PPE) for 8 days, and then stained the lipid droplets accumulated in the cytoplasm with Oil Red O. We also analyzed the effects of PPE on the mitogen-activated protein kinases (MAPKs) signaling, mitotic clonal expansion (MCE) and gene expressions associated with 3T3-L1 differentiation.ResultsWhen we cultured 3T3-L1 cells with PPE under differentiation conditions, the accumulation of lipid droplets and expression of adipocyte differentiation marker genes (Cebpa, Pparg, Slc2a4, Fasn and Adipoq) were dramatically attenuated. The suppressive activity of PPE against adipogenesis was heat-stable and recovered in a low-molecular-weight fraction after ultrafiltration (< 3 kDa) and gel-filtration chromatography (fraction No. 9). We also found that the suppressive activity of PPE affected the early phase of adipocyte differentiation (Days 0–2) without influencing the expression levels of C/EBPβ and C/EBPδ. The PPE and fraction No. 9 obtained from gel-filtration chromatography both promoted mitotic clonal expansion of 3T3-L1 while accelerating p38 MAPK phosphorylation. In addition, SB203580, a p38 MAPK inhibitor, partially restored the accumulation of lipid droplets and the expression of adipocyte differentiation marker genes that were suppressed by fraction No. 9.ConclusionThese results indicate that PPE suppresses the differentiation of preadipocytes via accelerated activation of p38 MAPK during the early phase of adipogenesis, suggesting PPE or its functional component could be a potential therapy for treating obesity.

【 授权许可】

CC BY