Phytol/Phytanic acid and insulin resistance: potential role of phytanic acid proven by docking simulation and modulation of biochemical alterations.

Since activation of PPARγ is the main target for the antidiabetic effect of TZDs, especially when it heterodimerizes with RXR, we aimed to test the potential antidiabetic effect of phytol (250 mg/kg), the natural precursor of phytanic acid, a RXR ligand and/or pioglitazone (5 mg/kg) to diabetic insu...

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Autores principales:	Mohamed M Elmazar, Hanan S El-Abhar, Mona F Schaalan, Nahla A Farag
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/81e7b34aaba04d0bb2ed63b28eaaed8a
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spelling	oai:doaj.org-article:81e7b34aaba04d0bb2ed63b28eaaed8a2021-11-18T08:02:57ZPhytol/Phytanic acid and insulin resistance: potential role of phytanic acid proven by docking simulation and modulation of biochemical alterations.1932-620310.1371/journal.pone.0045638https://doaj.org/article/81e7b34aaba04d0bb2ed63b28eaaed8a2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23300941/?tool=EBIhttps://doaj.org/toc/1932-6203Since activation of PPARγ is the main target for the antidiabetic effect of TZDs, especially when it heterodimerizes with RXR, we aimed to test the potential antidiabetic effect of phytol (250 mg/kg), the natural precursor of phytanic acid, a RXR ligand and/or pioglitazone (5 mg/kg) to diabetic insulin-resistant rats. Regarding the molecular docking simulation on PPARγ, phytanic acid, rather than phytol, showed a binding mode that mimics the crystal orientation of rosiglitazone and pioglitazone, forming H bonds with the same amino acids (S289, H 323, H 449 and Y 473), and the least energy level, which emphasizes their importance for PPARγ molecular recognition, activation, hence antidiabetic activity. In addition, docking on the RXRα/PPARγ heterodimer, revealed that phytanic acid has higher binding affinity and lesser energy score on RXRα, compared to the original ligand, retinoic acid. Phytanic acid binds by 3H bonds and shares retinoic acid in arginine (R 316). These results were further supported biochemically, where oral phytol and/or pioglitazone (5 mg/kg) improved significantly glucose homeostasis, lipid panel, raised serum adiponectin level and lowered TNF-α, reaching in most cases the effect of the 10 mg/kg pioglitazone. The study concluded that the insulin sensitizing/anti-diabetic effect of phytol is mediated by partly from activation of nuclear receptors and heterodimerization of RXR with PPARγ by phytanic acid.Mohamed M ElmazarHanan S El-AbharMona F SchaalanNahla A FaragPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e45638 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mohamed M Elmazar Hanan S El-Abhar Mona F Schaalan Nahla A Farag Phytol/Phytanic acid and insulin resistance: potential role of phytanic acid proven by docking simulation and modulation of biochemical alterations.
description	Since activation of PPARγ is the main target for the antidiabetic effect of TZDs, especially when it heterodimerizes with RXR, we aimed to test the potential antidiabetic effect of phytol (250 mg/kg), the natural precursor of phytanic acid, a RXR ligand and/or pioglitazone (5 mg/kg) to diabetic insulin-resistant rats. Regarding the molecular docking simulation on PPARγ, phytanic acid, rather than phytol, showed a binding mode that mimics the crystal orientation of rosiglitazone and pioglitazone, forming H bonds with the same amino acids (S289, H 323, H 449 and Y 473), and the least energy level, which emphasizes their importance for PPARγ molecular recognition, activation, hence antidiabetic activity. In addition, docking on the RXRα/PPARγ heterodimer, revealed that phytanic acid has higher binding affinity and lesser energy score on RXRα, compared to the original ligand, retinoic acid. Phytanic acid binds by 3H bonds and shares retinoic acid in arginine (R 316). These results were further supported biochemically, where oral phytol and/or pioglitazone (5 mg/kg) improved significantly glucose homeostasis, lipid panel, raised serum adiponectin level and lowered TNF-α, reaching in most cases the effect of the 10 mg/kg pioglitazone. The study concluded that the insulin sensitizing/anti-diabetic effect of phytol is mediated by partly from activation of nuclear receptors and heterodimerization of RXR with PPARγ by phytanic acid.
format	article
author	Mohamed M Elmazar Hanan S El-Abhar Mona F Schaalan Nahla A Farag
author_facet	Mohamed M Elmazar Hanan S El-Abhar Mona F Schaalan Nahla A Farag
author_sort	Mohamed M Elmazar
title	Phytol/Phytanic acid and insulin resistance: potential role of phytanic acid proven by docking simulation and modulation of biochemical alterations.
title_short	Phytol/Phytanic acid and insulin resistance: potential role of phytanic acid proven by docking simulation and modulation of biochemical alterations.
title_full	Phytol/Phytanic acid and insulin resistance: potential role of phytanic acid proven by docking simulation and modulation of biochemical alterations.
title_fullStr	Phytol/Phytanic acid and insulin resistance: potential role of phytanic acid proven by docking simulation and modulation of biochemical alterations.
title_full_unstemmed	Phytol/Phytanic acid and insulin resistance: potential role of phytanic acid proven by docking simulation and modulation of biochemical alterations.
title_sort	phytol/phytanic acid and insulin resistance: potential role of phytanic acid proven by docking simulation and modulation of biochemical alterations.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/81e7b34aaba04d0bb2ed63b28eaaed8a
work_keys_str_mv	AT mohamedmelmazar phytolphytanicacidandinsulinresistancepotentialroleofphytanicacidprovenbydockingsimulationandmodulationofbiochemicalalterations AT hananselabhar phytolphytanicacidandinsulinresistancepotentialroleofphytanicacidprovenbydockingsimulationandmodulationofbiochemicalalterations AT monafschaalan phytolphytanicacidandinsulinresistancepotentialroleofphytanicacidprovenbydockingsimulationandmodulationofbiochemicalalterations AT nahlaafarag phytolphytanicacidandinsulinresistancepotentialroleofphytanicacidprovenbydockingsimulationandmodulationofbiochemicalalterations
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Phytol/Phytanic acid and insulin resistance: potential role of phytanic acid proven by docking simulation and modulation of biochemical alterations.

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