Perfluorooctanoic acid binds to peroxisome proliferator-activated receptor γ and promotes adipocyte differentiation in 3T3-L1 adipocytes

Yamamoto, Junpei; Yamane, Takumi; Oishi, Yoshifumi; Kobayashi‐Hattori, Kazuo

doi:10.1080/09168451.2014.991683

Cited by 51 publications

(26 citation statements)

References 21 publications

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“…Regarding adipogenesis, the nuclear peroxisome proliferator-activated receptor gamma (PPAR-gamma) is an ultimate promoter of adipogenesis and hinders both osteoblastogenesis and myogenesis. The PPAR-gamma is also involved in adipocyte maturation and metabolism [63][64][65].…”

Section: Key Cellular and Endocrine Interactions Among Bone Muscle mentioning

confidence: 99%

Chronic Stress Contributes to Osteosarcopenic Adiposity via Inflammation and Immune Modulation: The Case for More Precise Nutritional Investigation

Ilich

Gilman²,

Cvijetić

et al. 2020

Nutrients

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Chronic stress and low-grade chronic inflammation (LGCI) are key underlying factors for many diseases, including bone and body composition impairments. Objectives of this narrative review were to examine the mechanisms by which chronic stress and LGCI may influence osteosarcopenic adiposity (OSA) syndrome, originally named as ostoesarcopenic obesity (OSO). We also examined the crucial nutrients presumed to be affected by or cause of stress and inflammation and compared/contrasted them to those of our prehistoric ancestors. The evidence shows that stress (particularly chronic) and its related inflammatory processes, contribute to osteoporosis, sarcopenia, and adiposity ultimately leading to OSA as a final and most deranged state of body composition, commencing at the mesenchymal cell lineage disturbance. The foods/nutrients consumed by modern humans, as well as their altered lifestyle, also contribute to stress, LGCI and subsequently to OSA. The processes can also go in opposite direction when stress and inflammation impact nutritional status, particularly some micronutrients’ levels. While nutritional management of body composition and LGCI have been studied, the nutrients (and their quantities) most affected by stressors and those which may act toward the alleviation of stressful state, ultimately leading to better body composition outcomes, need to be elucidated.

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Section: Key Cellular and Endocrine Interactions Among Bone Muscle mentioning

confidence: 99%

Chronic Stress Contributes to Osteosarcopenic Adiposity via Inflammation and Immune Modulation: The Case for More Precise Nutritional Investigation

Ilich

Gilman²,

Cvijetić

et al. 2020

Nutrients

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show abstract

“…PCB metabolites are high-affinity ligands for the thyroid hormone transport protein transthyretin (Cheek et al, 1999). p,p'-DDE binds to the androgen receptor (Kelce et al, 1995;Xu et al, 2013), while PFOA promotes adipocyte differentiation as a peroxisome proliferator-activated receptor gamma (PPARγ) ligand (White et al, 2011;Yamamoto et al, 2015). Several studies in rats demonstrated the thyroid-disrupting effect of the pesticides DDT (Scollon et al, 2004) and HCB (Alvarez et al, 2005;van Raaij et al, 1993a;van Raaij et al, 1993b), as they decreased serum levels of thyroid hormones.…”

Section: Mechanismsmentioning

confidence: 99%

Prenatal exposure to endocrine disrupting chemicals and risk of being born small for gestational age: Pooled analysis of seven European birth cohorts

Govarts

Iszatt

Trnovec

et al. 2018

Environment International

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“…Perfluorinated alkylic acids (PFAAs) are documented to bind to and/or interact with many proteins, potentially interfering with their normal physiological function. This includes serum albumin (SA) that acts as blood fatty acid transporter system [9], and proteins highly expressed in the liver, such as liver fatty acid binding protein (L-FABP) that is responsible for fatty acid uptake, transport and metabolism [10] and peroxime proliferated-activated receptors alpha and gamma (PPARα and PPARγ) [11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Prediction of Accurate Binding Modes using Combination of classical and accelerated Molecular dynamics and Free Energy Perturbation Calculations: An Application to Toxicity Studies

Fratev

Steinbrecher

Jónsdóttir³

2018

Preprint

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Estimating the correct binding modes of ligands in protein-ligand complexes is not only crucial in the drug discovery process, but also for elucidating potential toxicity mechanisms. In the current paper, we discuss and demonstrate a computational modelling protocol using the combination of docking, classical (cMD) and accelerated (aMD) molecular dynamics and free energy perturbation (FEP+ protocol) for identification of the binding modes of selected perfluorocarboxyl acids (PFCAs) in the PPARγ nuclear receptor.Initially, we employed both the regular and induced fit docking which failed to correctly predict the ligand binding modes and rank the compounds with respect to experimental free energies of binding, when they were docked into non-native X-ray structure. The cMD and aMD simulations identified the presence of multiple binding modes for these compounds, and the shorter chain PFCAs (C6-C8) continuously moved between a few energetically favourable binding conformations. These results demonstrate that the docking scoring function cannot rank compounds precisely in such cases, not due to its insufficiency, but because of the use of incorrect or only one unique bindings pose, neglecting the protein dynamics. Finally, based on MD predictions of binding conformations, the FEP+ sampling protocol was extended and then accurately reproduced experimental differences in the free energies.Thus, the preliminary MD simulations can also provide helpful information about correct set-up of the . 20, 2018; 2 FEP+ calculations. These results show that the PFCAs binding modes were accurately predicted and the FEP+ protocol can be used to estimate free energies of binding of flexible molecules outside of typical drug-like compounds. CC-BY-NC-ND4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/251058 doi: bioRxiv preprint first posted online Jan.Our in silico workflow revealed the main characteristics of the PFCAs, which are week PPARγ partial agonists and illustrated the importance of specific ligand-residue interactions within the LBD. This work also suggests a common workflow for identification of ligand binding modes, ligand-protein dynamics description and relative free energy calculations.

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Perfluorooctanoic acid binds to peroxisome proliferator-activated receptor γ and promotes adipocyte differentiation in 3T3-L1 adipocytes

Cited by 51 publications

References 21 publications

Chronic Stress Contributes to Osteosarcopenic Adiposity via Inflammation and Immune Modulation: The Case for More Precise Nutritional Investigation

Chronic Stress Contributes to Osteosarcopenic Adiposity via Inflammation and Immune Modulation: The Case for More Precise Nutritional Investigation

Prenatal exposure to endocrine disrupting chemicals and risk of being born small for gestational age: Pooled analysis of seven European birth cohorts

Prediction of Accurate Binding Modes using Combination of classical and accelerated Molecular dynamics and Free Energy Perturbation Calculations: An Application to Toxicity Studies

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