A metabolite of daidzein, 6,7,4′‐trihydroxyisoflavone, suppresses adipogenesis in 3<scp>T</scp>3‐<scp>L</scp>1 preadipocytes via <scp>ATP</scp>‐competitive inhibition of <scp>PI</scp>3<scp>K</scp>

Seo, Soonmin; Yang, Hee Seok; Shin, Seung Ho; Min, Soyun; Kim, Yeong A; Yu, Jae Gak; Lee, Dong‐Eun; Chung, Min‐Yu; Heo, Yong‐Seok; Kwon, Jung Yeon; Yue, Shuhua; Kim, Kee Hong; Cheng, Ji‐Xin; Lee, Ki Won; Lee, Hyong Joo

doi:10.1002/mnfr.201200593

Cited by 35 publications

(34 citation statements)

References 47 publications

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“…Endogenous β-glucosidase in soybean is reported to be able to convert isoflavone glucosides into aglycones, in agreement with the increase in the amount of isoflavone aglycones and decrease in isoflavone glucosides during soybean soaking in water and processing [17]. Previous studies have demonstrated that isoflavones have anti-obesity or anti-adipogenesis function by suppressing obesity-related transcription through a feedback mechanism on adiponectin, adipoR1, adipoR2, and 5′ adenosine monophosphate-activated protein kinase (AMPK), or by targeting the PI3K/AKT signaling pathway [18,19]. Therefore, we suggest that isoflavone-rich BSK extract may also have similar functions against adipogenesis or insulin resistance.…”

Section: Resultsmentioning

confidence: 53%

Effect of Black Soybean Koji Extract on Glucose Utilization and Adipocyte Differentiation in 3T3-L1 Cells

Huang

Hou

et al. 2014

IJMS

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Adipocyte differentiation and the extent of subsequent fat accumulation are closely related to the occurrence and progression of diseases such as insulin resistance and obesity. Black soybean koji (BSK) is produced by the fermentation of black soybean with Aspergilllus awamori. Previous study indicated that BSK extract has antioxidative and multifunctional bioactivities, however, the role of BSK in the regulation of energy metabolism is still unclear. We aimed to investigate the effect of glucose utilization on insulin-resistant 3T3-L1 preadipocytes and adipogenesis-related protein expression in differentiated adipocytes with BSK treatment. Cytoxicity assay revealed that BSK did not adversely affect cell viability at levels up to 200 μg/mL. The potential for glucose utilization was increased by increased glucose transporter 1 (GLUT1), GLUT4 and protein kinase B (AKT) protein expression in insulin-resistant 3T3-L1 cells in response to BSK treatment. Simultaneously, BSK inhibited lipid droplet accumulation in differentiated 3T3-L1 cells. The inhibitory effect of adipogenesis was associated with downregulated peroxisome proliferator-activated receptor γ (PPARγ) level and upregulated Acrp30 protein expression. Our results suggest that BSK extract could improve glucose uptake by modulating GLUT1 and GLUT4 expression in a 3T3-L1 insulin-resistance cell model. In addition, BSK suppressed differentiation and lipid accumulation in mature 3T3-L1 adipocytes, which may suggest its potential for food supplementation to prevent obesity and related metabolic abnormalities.

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Section: Resultsmentioning

confidence: 53%

Effect of Black Soybean Koji Extract on Glucose Utilization and Adipocyte Differentiation in 3T3-L1 Cells

Huang

Hou

et al. 2014

IJMS

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“…A kinase assay was performed as previously described [Seo et al, ]. Briefly, active PI3K protein (100 ng) was incubated with HST, at volumes of 20, 40, and 80 µM, or PI3K inhibitor LY294002 (20 µM), before 20 µl phosphatidylinositol (0.5 mg/ml; Avanti Polar Lipids, Alabaster, AL) was added.…”

Section: Methodsmentioning

confidence: 99%

Hirsutenone Directly Targets PI3K and ERK to Inhibit Adipogenesis in 3T3‐L1 Preadipocytes

Cheong

Suk

Thimmegowda

et al. 2015

J of Cellular Biochemistry

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Adipogenesis is a key driver of the expansion of adipose tissue mass that causes obesity. Hirsutenone (HST) is an active botanical diarylheptanoid present in Alnus species. In this study, we evaluated the effects of HST on adipogenesis, its mechanisms of action and the molecular targets involved. Using Oil Red O staining, we observed that HST dose-dependently suppresses lipid accumulation during adipogenesis in 3T3-L1 preadipocytes, concomitant with a decrease in peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα) and fatty acid synthase (FAS) protein expression. This inhibitory effect was largely limited to the early stage of adipogenesis, which includes mitotic clonal expansion (MCE), as evidenced by delayed cell cycle entry of preadipocytes from G1 to S phase. Furthermore, the regulation of MCE was accompanied by suppression of phosphatidylinositol 3-kinase (PI3K) and extracellular-regulated kinase (ERK) activity. HST was also shown to bind directly to PI3K and ERK1 in a non-ATP competitive manner. Our results suggest that HST attenuates adipogenesis by directly targeting PI3K and ERK during MCE in 3T3-L1 preadipocytes, underscoring the potential therapeutic application of HST in preventing obesity.

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“…Recently, Seo et al reported that 6-OHD at high concentrations (40 to 80 μM) suppressed adipogenesis in 3T3-L1 preadipocytes by directing targeting phosphatidylinositol 3-kinase (PI3K) [70]. In contrast, Chen et al recently reported that 6-OHD at low concentrations (10 to 20 μM) significantly promoted 3T3-L1 preadipocytes differentiation [71].…”

Section: Bioactivity Of Ohd and Ohgmentioning

confidence: 99%

Isolation, Bioactivity, and Production of ortho-Hydroxydaidzein and ortho-Hydroxygenistein

Chang

2014

IJMS

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Daidzein and genistein are two major components of soy isoflavones. They exist abundantly in plants and possess multiple bioactivities. In contrast, ortho-hydroxydaidzein (OHD) and ortho-hydroxygenistein (OHG), including 6-hydroxydaidzein (6-OHD), 8-hydroxydaidzein (8-OHD), 3′-hydroxydaidzein (3′-OHD), 6-hydroxygenistein (6-OHG), 8-hydroxygenistein (8-OHG), and 3′-hydroxygenistein (3′-OHG), are rarely found in plants. Instead, they are usually isolated from fermented soybean foods or microbial fermentation broth feeding with soybean meal. Accordingly, the bioactivity of OHD and OHG has been investigated less compared to that of soy isoflavones. Recently, OHD and OHG were produced by genetically engineering microorganisms through gene cloning of cytochrome P450 (CYP) enzyme systems. This success opens up bioactivity investigation and industrial applications of OHD and OHG in the future. This article reviews isolation of OHD and OHG from non-synthetic sources and production of the compounds by genetically modified microorganisms. Several bioactivities, such as anticancer and antimelanogenesis-related activities, of OHD and OHG, are also discussed.

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A metabolite of daidzein, 6,7,4′‐trihydroxyisoflavone, suppresses adipogenesis in 3T3‐L1 preadipocytes via ATP‐competitive inhibition of PI3K

Abstract: Our results suggest that 6,7,4'-THIF suppresses adipogenesis in 3T3-L1 preadipocytes by directly targeting PI3K. Soy isoflavones like 6,7,4'-THIF may have potential for development into novel treatment strategies for chronic obesity.

Cited by 35 publications

References 47 publications

Effect of Black Soybean Koji Extract on Glucose Utilization and Adipocyte Differentiation in 3T3-L1 Cells

Effect of Black Soybean Koji Extract on Glucose Utilization and Adipocyte Differentiation in 3T3-L1 Cells

Hirsutenone Directly Targets PI3K and ERK to Inhibit Adipogenesis in 3T3‐L1 Preadipocytes

Isolation, Bioactivity, and Production of ortho-Hydroxydaidzein and ortho-Hydroxygenistein

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