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Low-intensity pulsed ultrasound suppresses proliferation and promotes apoptosis via p38 MAPK signaling in rat visceral preadipocytes.

ABSTRACT: Low-intensity pulsed ultrasound (LIPUS) has been used widely in clinical therapy for bone fracture and soft tissue injury. However, whether LIPUS regulates primary preadipocyte function and adipogenesis remains unknown. In this study, we investigated the potential role of LIPUS in regulating visceral preadipocyte function. Resuspended rat visceral preadipocytes were treated with LIPUS (0.5 MHz, 109.44 mW/cm2) for 1 min and then cultured for an additional 48 hours. Cell proliferation was examined using the CCK-8 assay, and the early apoptosis rate was determined by flow cytometry. In addition, we evaluated the related signaling pathway via examination of proliferating cell nuclear antigen (PCNA), peroxisome proliferator-activated receptor gamma (PPAR?), Bcl2, Bax, cleaved caspase 3 (C-C3), and mitogen-activated protein kinase (MAPK) member protein levels using western blot or quantitative real-time PCR (qRT-PCR). LIPUS inhibited preadipocyte proliferation and induced cell apoptosis. The protein expression of proliferation markers decreased, while expression of the apoptosis-related modulators increased following LIPUS treatment. LIPUS treatment decreased extracellular signal-regulated kinase (ERK) phosphorylation and increased p38 MAPK phosphorylation. Inhibition of p38 MAPK rescued the LIPUS-induced proliferation inhibition and apoptosis induction. Thus, treatment of rat visceral preadipocytes with 0.5 MHz LIPUS suppresses proliferation and promotes apoptosis via activation of p38 MAPK signaling.

SUBMITTER: Xu T

PROVIDER: S-EPMC5883135 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Low-intensity pulsed ultrasound suppresses proliferation and promotes apoptosis via p38 MAPK signaling in rat visceral preadipocytes.

Xu Tianhua T Gu Jia J Li Chenghai C Guo Xiasheng X Tu Juan J Zhang Dong D Sun Wei W Kong Xiangqing X

American journal of translational research 20180315 3

Low-intensity pulsed ultrasound (LIPUS) has been used widely in clinical therapy for bone fracture and soft tissue injury. However, whether LIPUS regulates primary preadipocyte function and adipogenesis remains unknown. In this study, we investigated the potential role of LIPUS in regulating visceral preadipocyte function. Resuspended rat visceral preadipocytes were treated with LIPUS (0.5 MHz, 109.44 mW/cm<sup>2</sup>) for 1 min and then cultured for an additional 48 hours. Cell proliferation w ...[more]

PMID: 29636884

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Project description: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.

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Low-intensity pulsed ultrasound suppresses proliferation and promotes apoptosis via p38 MAPK signaling in rat visceral preadipocytes.

Publications

Low-intensity pulsed ultrasound suppresses proliferation and promotes apoptosis via p38 MAPK signaling in rat visceral preadipocytes.

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