Molecular mechanism of down-regulating adipogenic transcription factors in 3T3-L1 adipocyte cells by bioactive anti-adipogenic compounds

Guru, Ajay; Issac, Praveen Kumar; Velayutham, Manikandan; Saraswathi, N.T.; Arshad, Aziz; Arockiaraj, Jesu

doi:10.1007/s11033-020-06036-8

Cited by 61 publications

(34 citation statements)

References 107 publications

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“…In addition, due to the local adverse effects of anti-glaucoma medications, significant attention has been paid to the issue of prostaglandin (PG)-induced peri-orbitopathy, such as the deepening of the upper eyelid sulcus (DUES) [ 21 , 22 ]. Recently, to study these anti-glaucoma medications for use in treating periocular tissues, especially orbital fatty tissues, the 3T3-L1 cell, a most frequently used preadipocyte cell line for adipogenesis related studies, has also been used [ 23 ]. Therefore, taking these similarities between ROCK-is and EP2 agonists toward the adipogenesis of the 3T3-L1 cells into account, it would be of great interest to learn more regarding the simultaneous effects of these materials, and this may rationally become the fundamental basis for estimating what would happen in cases where these drugs are clinically used together.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Use of ROCK Inhibitors and EP2 Agonists Induces Unexpected Effects on Adipogenesis and the Physical Properties of 3T3-L1 Preadipocytes

Ida

Watanabe

Ohguro

et al. 2021

IJMS

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To elucidate the additive effects of an EP2 agonist, omidenepag (OMD) or butaprost (Buta) on the Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor, ripasudil (Rip) on adipose tissue, two- or three-dimension (2D or 3D) cultures of 3T3-L1 cells were analyzed by lipid staining, the mRNA expression of adipogenesis-related genes, extracellular matrix (ECM) molecules including collagen (Col) -1, -4 and -6, and fibronectin (Fn), and the sizes and physical properties of 3D organoids, as measured by a micro-squeezer. The results indicate that adipogenesis induced (1) an enlargement of the 3D organoids; (2) a substantial enhancement in lipid staining as well as the expression of the Pparγ, Ap2 and Leptin genes; (3) a significant softening of the 3D organoids, the effects of which were all enhanced by Rip except for Pparγ expression; and (4) a significant downregulation in Col1 and Fn, and a significant upregulation in Col4, Col6, the effects of which were unchanged by Rip. When adding the EP2 agonist to Rip, (1) the sizes of the 3D organoids were reduced substantially; (2) lipid staining was increased (OMD), or decreased (Buta); (3) the stiffness of the 3D organoids was substantially increased in Buta; (4-1) the expression of Pparγ was suppressed (2D, OMD) or increased (2D, Buta), and the expressions of Ap2 were downregulated (2D, 3D) and Leptin was increased (2D) or decreased (3D), (4-2) all the expressions of four ECM molecules were upregulated in 2D (2D), and in 3D, the expression of Col1, Col4 was upregulated. The collective findings reported herein indicate that the addition of an EP2 agonist, OMD or Buta significantly but differently modulate the Rip-induced effects on adipogenesis and the physical properties of 2D and 3D cultured 3T3-L1 cells.

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Section: Introductionmentioning

confidence: 99%

Simultaneous Use of ROCK Inhibitors and EP2 Agonists Induces Unexpected Effects on Adipogenesis and the Physical Properties of 3T3-L1 Preadipocytes

Ida

Watanabe

Ohguro

et al. 2021

IJMS

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“…AMPK acts as a central modulator of energy sensing and homeostasis [ 11 ]. Phosphorylated AMPK promotes catabolic pathways such as fatty acid oxidation and inhibits energy consumption pathways such as fatty acid synthesis [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

“…The activation of ERK is essential for inducing adipogenesis and the necessary differentiation process called mitotic clonal expansion [ 45 ]. Adipocyte differentiation was promoted by the activation of several kinases, specifically PI3K kinase, activating p38, resulting in adipocyte synthesis [ 11 ]. Both compounds reduced the phosphorylation of ERK and p38 in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

“…To overcome these problems, studies on the anti-obesity effects of various natural bioactive compounds quercetin, kaempferol, and gallic acid have been conducted. These bioactive components reduced adipose tissue mass by promoting lipolysis, inhibiting adipose tissue development, and preadipocyte differentiation [ 11 ]. Further research in this field will be an excellent alternative treatment strategy for developing effective and safe anti-obesity drugs in the future.…”

Section: Introductionmentioning

confidence: 99%

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Saikosaponin A and D Inhibit Adipogenesis via the AMPK and MAPK Signaling Pathways in 3T3-L1 Adipocytes

Lim

Lee

Han

et al. 2021

IJMS

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Obesity is a lipid metabolism disorder caused by genetic, medicinal, nutritional, and other environmental factors. It is characterized by a complex condition of excess lipid accumulation in adipocytes. Adipogenesis is a differentiation process that converts preadipocytes into mature adipocytes and contributes to excessive fat deposition. Saikosaponin A (SSA) and saikosaponin D (SSD) are triterpenoid saponins separated from the root of the Bupleurum chinensis, which has long been used to treat inflammation, fever, and liver diseases. However, the effects of these constituents on lipid accumulation and obesity are poorly understood. We investigated the anti-obesity effects of SSA and SSD in mouse 3T3-L1 adipocytes. The MTT assay was performed to measure cell viability, and Oil Red O staining was conducted to determine lipid accumulation. Various adipogenic transcription factors were evaluated at the protein and mRNA levels by Western blot assay and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Here, we showed that SSA and SSD significantly inhibited lipid accumulation without affecting cell viability within the range of the tested concentrations (0.938–15 µM). SSA and SSD also dose-dependently suppressed the expression of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein alpha (C/EBPα), sterol regulatory element binding protein-1c (SREBP-1c), and adiponectin. Furthermore, the decrease of these transcriptional factors resulted in the repressed expression of several lipogenic genes including fatty acid binding protein (FABP4), fatty acid synthase (FAS), and lipoprotein lipase (LPL). In addition, SSA and SSD enhanced the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase (ACC), and inhibited the phosphorylation of extracellular-regulated kinase 1/2 (ERK1/2) and p38, but not c-Jun-N-terminal kinase (JNK). These results suggest that SSA and SSD inhibit adipogenesis through the AMPK or mitogen-activated protein kinase (MAPK) pathways in the early stages of adipocyte differentiation. This is the first study on the anti-adipogenic effects of SSA and SSD, and further research in animals and humans is necessary to confirm the potential of saikosaponins as therapeutic agents for obesity.

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“…Abdul et al [22] explained the cytotoxicity of crude methanolic leaf extract of A. indicum. In brine shrimp lethality bioassay, LC 50 obtained from the best-fit line slope were 0.419, 3.01, 5.62, 1.51, and 11.20 μg/ml [21].…”

Section: Introductionmentioning

confidence: 99%

Study of in vitro activity on glucose uptake of 3T3L1 cells, RIN5f cells, and glycemic index stimulation inhibitory effect of Abutilon indicum (L.) extract

Lavanya¹,

Veeraraghavan²,

Renuka³

et al. 2022

J Appl Biol Biotech

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Abutilon indicum (L.) is one of the traditional medicinal plants and its extract has been utilized for antidiabetic activity. Diabetes mellitus is a metabolic disorder characterized by hyperglycemia and its occurrence is increasing fast in most countries. Peroxisome proliferator-activated receptor gamma (PPARγ) plays an important role in adipogenesis. The present study determines the effect of A. indicum methanolic leaf extract as potential antidiabetic inhibitors. The in vitro analysis was carried out by using 3T3L1 for glucose uptake assay, RIN5F cell lines for insulin secretion, hydrolysis assay to predict glycemic index, 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging assay, and molecular interaction of the known bioactive compounds with PPARγ. The experimental results showed 100 nM insulin and 50 mM LiCl glucose uptake with 3.37 and 3.86 fold stimulation, respectively, when compared to the control, whereas the given samples of 200, 400, and 800 µg/ml showed 1.37, 1.62, and 1.85 µg/ml fold stimulation, respectively, when compared to the control. The insulin release in RIN-5f cells was observed with a positive control and crude extract and the results showed 4.67 and 2.67 µg/ml, respectively. The hydrolysis index value was found to be 53.30 and the glycemic load was 17.48 µg/ml. In the DPPH assay, the sample showed dose-dependent DPPH radical scavenging activity with an IC 50 value of 99.12 µg/ml when compared to standard quercetin with an IC 50 value of 1.7 µg/ml. The molecular interaction of PPARγ and active methyl trans-p-coumarate (−5.44) > methyl caffeate (−4.49) > syringic acid (−3.9) > pinellic acid (−2.62) compared with thiazolidinediones (−7.62) formed a novel type of oral antidiabetic medication that improved metabolic management in type 2 diabetic patients by increasing insulin sensitivity. The overall result shows that A. indicum (L.) is a potential indicator for sensitizing insulin secretion and strongly inhibits the release of glucagon which can be used as a therapeutic agent for treating and managing diabetes.

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Molecular mechanism of down-regulating adipogenic transcription factors in 3T3-L1 adipocyte cells by bioactive anti-adipogenic compounds

Cited by 61 publications

References 107 publications

Simultaneous Use of ROCK Inhibitors and EP2 Agonists Induces Unexpected Effects on Adipogenesis and the Physical Properties of 3T3-L1 Preadipocytes

Simultaneous Use of ROCK Inhibitors and EP2 Agonists Induces Unexpected Effects on Adipogenesis and the Physical Properties of 3T3-L1 Preadipocytes

Saikosaponin A and D Inhibit Adipogenesis via the AMPK and MAPK Signaling Pathways in 3T3-L1 Adipocytes

Study of in vitro activity on glucose uptake of 3T3L1 cells, RIN5f cells, and glycemic index stimulation inhibitory effect of Abutilon indicum (L.) extract

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