Quizalofop-p-Ethyl Induces Adipogenesis in 3T3-L1 Adipocytes

Biserni, Martina; Mesnage, Robin; Ferro, R.; Wozniak, Eva; Xenakis, Theodoros; Mein, Charles A.; Antoniou, Michael

doi:10.1093/toxsci/kfz097

Cited by 24 publications

(18 citation statements)

References 39 publications

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“…Activation of PPARγ by the ligand enhances adipogenesis and lipogenesis. In the process of adipogenesis, pre-adipocytes develop into mature adipocytes which contain more lipids [29]. In this study, we investigated the ability of GS1, GS2, and GS3 to exert weaker lipogenic effect as promising therapeutic agents to treat insulin resistance without adiposity.…”

Section: Discussionmentioning

confidence: 99%

A Novel Partial PPARγ Agonist Has Weaker Lipogenic Effect in Adipocytes and Stimulates GLUT4 Translocation in Skeletal Muscle Cells via AMPK-Dependent Signaling

et al. 2021

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Introduction: Peroxisome proliferator-activated receptor gamma (PPARγ) agonists are highly effective in treating insulin resistance. However, associated side effects such as weight gain due to increase in adipogenesis and lipogenesis hinder their clinical use. The aim of the study was to design and synthesize novel partial PPARγ agonists with weaker lipogenic effect in adipocytes and enhanced glucose transporter 4 (GLUT4) translocation stimulatory effect in skeletal muscle cells. Methods: Novel partial PPARγ agonists (GS1, GS2, and GS3) were designed and screened to predict their binding interactions with PPARγ by molecular docking. The stability of the docked ligand-PPARγ complex was studied by molecular dynamics (MD) simulation. The cytotoxicity of synthesized compounds was tested in 3T3-L1 adipocytes and L6 myoblasts by MTT assay. The lipogenic effect was investigated in 3T3-L1 adipocytes using oil red O staining and GLUT4 translocation stimulatory effect in L6-GLUT4myc myotubes by an antibody-coupled colorimetric assay. Results: The molecular docking showed the binding interactions between designed agonists and PPARγ. MD simulation demonstrated good stability between the GS2-PPARγ complex. GS2 and GS3 did not show any significant effect on cell viability up to 80 or 100 μM concentration. Pioglitazone treatment significantly increased intracellular lipid accumulation in adipocytes compared to control. However, this effect was significantly less in GS2- and GS3-treated conditions compared to pioglitazone at 10 μM concentration, indicating weaker lipogenic effect. Furthermore, GS2 significantly stimulated GLUT4 translocation to the plasma membrane in a dose-dependent manner via the AMPK-dependent signaling pathway in skeletal muscle cells. Conclusion: GS2 may be a promising therapeutic agent for the treatment of insulin resistance and type 2 diabetes mellitus without adiposity.

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Section: Discussionmentioning

confidence: 99%

A Novel Partial PPARγ Agonist Has Weaker Lipogenic Effect in Adipocytes and Stimulates GLUT4 Translocation in Skeletal Muscle Cells via AMPK-Dependent Signaling

et al. 2021

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“…Available glucose-lowering drugs are unable to control hyperlipidemia. Furthermore, the peroxisome proliferator-activated receptor-gamma (PPARγ) agonists (e.g., rosiglitazone) are reported to promote adipogenesis [ 28 , 29 ]. For this reason, there is a growing interest to identify novel bioactive compounds that have the capacity to increase insulin sensitivity and lower lipid levels simultaneously.…”

Section: Discussionmentioning

confidence: 99%

The Powdered Root of Eurycoma longifolia Jack Improves Beta-Cell Number and Pancreatic Islet Performance through PDX1 Induction and Shows Antihyperglycemic Activity in db/db Mice

Tsai

Fang

Liao³

et al. 2020

Nutrients

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Non-insulin-dependent diabetes mellitus (NIDDM) is a common metabolic disorder worldwide. In addition to the chief feature of long-standing hyperglycemia, dyslipidemia, hyperinsulinemia, and a number of complications develop in parallel. It is believed that an adequate control of blood glucose levels can cause these complications to go into remission. This study was performed to evaluate the antidiabetic activity of Eurycoma longifolia Jack (EL) in vivo. The blood-glucose-lowering activity of EL was studied in db/db mice administered crude powdered EL root (25, 50, and 100 mg/kg) orally for eight weeks. At the end of the study, HbA1c, insulin, plasma lipid levels, and histopathology were performed. Powdered EL root showed significant antihyperglycemic activity along with the control of body weight. After eight weeks of treatment, both the blood cholesterol level and the glycogen deposit in hepatocytes were remarkably lower, whereas the secreting insulin level was elevated. An improvement in islet performance was manifested as an increase in beta-cell number and pancreatic and duodenal homeobox 1 (PDX1) expression. Neogenesis or formation of new islets from pancreatic duct epithelial cells seen in the EL-treated group was encouraging. This study confirms the antihyperglycemic activity of EL through PDX1-associated beta-cell expansion resulting in an enhancement of islet performance.

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“…The widely used and controversial herbicide, glyphosate, induced obesity in F2 and F3 offspring of F0 female rats exposed during gestation ( 101 ). Many other agrochemicals induced adipogenesis in 3T3-L1 preadipocytes and in mouse and human MSCs ( 75 , 76 , 148 ). While the potential of these chemicals to promote obesity, in vivo , remains unexplored at present, the next chemical found to induce adipogenesis in cell models but that fails to promote obesity, in vivo , will be the first.…”

Section: Obesogens Old and Newmentioning

confidence: 99%

Obesity and endocrine-disrupting chemicals

Amato

Wheeler

Blumberg

2021

Endocrine Connections

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Obesity is now a worldwide pandemic. The usual explanation given for the prevalence of obesity is that it results from consumption of a calorie dense diet coupled with physical inactivity. However, this model inadequately explains rising obesity in adults and in children over the past few decades, indicating that other factors must be important contributors. An Endocrine-Disrupting Chemical (EDC) is an exogenous chemical, or mixture that interferes with any aspect of hormone action. EDCs have become pervasive in our environment, allowing humans to be exposed daily through ingestion, inhalation, and direct dermal contact. Exposure to EDCs has been causally linked with obesity in model organisms and associated with obesity occurrence in humans. Obesogens are chemicals, including some EDCs that promote adipogenesis and obesity, in vivo, by a variety of mechanisms. The environmental obesogen model holds that exposure to obesogens elicits a predisposition to obesity and that such exposures may be an important yet overlooked factor in the obesity pandemic. Effects produced by EDCs and obesogen exposure may be passed to subsequent, unexposed generations. This “generational toxicology” is not currently factored into risk assessment by regulators but may be another important factor in the obesity pandemic as well as in the worldwide increases in the incidence of noncommunicable diseases that plague populations everywhere. This review addresses the current evidence on how obesogens affect body mass, discusses long-known chemicals that have been more recently identified as obesogens, and how the accumulated knowledge can help identify EDCs hazards.

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Quizalofop-p-Ethyl Induces Adipogenesis in 3T3-L1 Adipocytes

Cited by 24 publications

References 39 publications

A Novel Partial PPARγ Agonist Has Weaker Lipogenic Effect in Adipocytes and Stimulates GLUT4 Translocation in Skeletal Muscle Cells via AMPK-Dependent Signaling

A Novel Partial PPARγ Agonist Has Weaker Lipogenic Effect in Adipocytes and Stimulates GLUT4 Translocation in Skeletal Muscle Cells via AMPK-Dependent Signaling

The Powdered Root of Eurycoma longifolia Jack Improves Beta-Cell Number and Pancreatic Islet Performance through PDX1 Induction and Shows Antihyperglycemic Activity in db/db Mice

Obesity and endocrine-disrupting chemicals

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