Tubby-like protein superfamily member PLSCR3 functions as a negative regulator of adipogenesis in mouse 3T3-L1 preadipocytes by suppressing induction of late differentiation stage transcription factors

Inokawa, Akira; Inuzuka, Tatsutoshi; Takahara, Taishi; Shibata, Hideki; Maki, Masatoshi

doi:10.1042/bsr20150215

Cited by 6 publications

(6 citation statements)

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“…It is well known that various morphologic and genetic changes occur during adipocyte maturation, and the adipogenesis of the cells is divided into two phases, an early phase from day 0 to day 2 and a late phase from day 3 to day 8 [36, 37]. In order to examine the effects of PPE on the two phases, we added fraction No.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2019

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Background Adipogenesis, 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. Method We 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. Results When 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. Conclusion These 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. Electronic supplementary material The online version of this article (10.1186/s12986-019-0361-8) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

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

et al. 2019

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“…PLSCR3 gene knockout ( Plscr3 −/− ) mice accumulated abdominal fat and displayed insulin resistance and glucose intolerance [ 109 ]. On the other hand, overexpression of PLSCR3 inhibited the adipogenesis of mouse 3T3-L1 cells by suppressing induction of the mRNAs of late stage pro-adipogenic transcription factors [ 110 ]. The biological significance of ALG-2 binding to the N-terminal PRR of PLSCR3 has not been clarified.…”

Section: Interacting Protein Network Of Alg-2 In Membrane Traffickmentioning

confidence: 99%

Multifaceted Roles of ALG-2 in Ca2+-Regulated Membrane Trafficking

Maki

Takahara

Shibata

2016

IJMS

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ALG-2 (gene name: PDCD6) is a penta-EF-hand Ca2+-binding protein and interacts with a variety of proteins in a Ca2+-dependent fashion. ALG-2 recognizes different types of identified motifs in Pro-rich regions by using different hydrophobic pockets, but other unknown modes of binding are also used for non-Pro-rich proteins. Most ALG-2-interacting proteins associate directly or indirectly with the plasma membrane or organelle membranes involving the endosomal sorting complex required for transport (ESCRT) system, coat protein complex II (COPII)-dependent ER-to-Golgi vesicular transport, and signal transduction from membrane receptors to downstream players. Binding of ALG-2 to targets may induce conformational change of the proteins. The ALG-2 dimer may also function as a Ca2+-dependent adaptor to bridge different partners and connect the subnetwork of interacting proteins.

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“…We focused on CCAAT/enhancer-binding proteins (C/EBPs), forkhead transcription factor 1 (FoxO1), and peroxisome proliferator-activated receptor-gamma (PPAR-γ) transcription factors as the markers of adipocyte differentiation as well as adiponectin. C/EBPs are a family of six gene members, among which C/EBP-δ and C/EBP-β are expressed at the early stage, and C/EBP-α or PPAR-γ are expressed at the late stage of adipocyte differentiation [10,11]. Knockdown of either C/EBP-δ or C/EBP-β (in combination or independently) suppresses the differentiation of primary embryonic fibroblasts into mature adipocytes and lipid accumulation [12].…”

Section: Introductionmentioning

confidence: 99%

Paeonol, an Ingredient of Kamishoyosan, Reduces Intracellular Lipid Accumulation by Inhibiting Glucocorticoid Receptor Activity in 3T3-L1 Cells

et al. 2020

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Excessive triglyceride accumulation in lipid-metabolizing tissues is associated with an increased risk of a variety of metabolic diseases. Kamishoyosan (KSS) is a Kampo composed of 10 constituent herbs, and contains moutan cortex (MC) and paeonol (PN) as the major ingredient of MC. Here, we demonstrate the molecular mechanism underlying the effect of KSS on the differentiation of mouse preadipocytes (3T3-L1 cells). KSS inhibited the accumulation of triglycerides in a dose-dependent manner in 3T3-L1 cells that were induced to differentiate into adipocytes. We also found that MC and PN were responsible for the anti-adipogenetic effect of KSS and significantly suppressed the expression of CCAAT/enhancer-binding proteins-δ (C/EBP-δ) mRNA 3 days after the induction of differentiation. Thus, PN may contribute to the anti-adipogenetic property of MC in 3T3-L1 cells. In addition, PN inhibited dexamethasone (Dex)-induced glucocorticoid receptor (GR) promoter activity. Taken together, these results suggest that PN suppresses C/EBP-δ expression by inhibiting Dex-induced GR promoter activity at the early stage of differentiation and, consequently, delays differentiation into mature adipocytes. Our results suggest that the habitual intake of Kampo-containing PN contributes to the prevention of the onset of metabolic diseases by decreasing the excessive accumulation of triglycerides in lipid-metabolizing tissues.

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Tubby-like protein superfamily member PLSCR3 functions as a negative regulator of adipogenesis in mouse 3T3-L1 preadipocytes by suppressing induction of late differentiation stage transcription factors

Cited by 6 publications

References 59 publications

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

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

Multifaceted Roles of ALG-2 in Ca2+-Regulated Membrane Trafficking

Paeonol, an Ingredient of Kamishoyosan, Reduces Intracellular Lipid Accumulation by Inhibiting Glucocorticoid Receptor Activity in 3T3-L1 Cells

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