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PloS One 2013Since 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...
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.
Topics: Algorithms; Animals; Catalytic Domain; Crystallography, X-Ray; Dimerization; Hydrogen Bonding; Insulin Resistance; Ligands; Male; Molecular Docking Simulation; PPAR gamma; Phytanic Acid; Phytol; Protein Binding; Rats; Rats, Wistar; Retinoid X Receptor alpha; Software
PubMed: 23300941
DOI: 10.1371/journal.pone.0045638 -
Nutrients Nov 2023Vitamin K (VK), a fat-soluble vitamin, is essential for the clotting of blood because of its role in the production of clotting factors in the liver. Moreover,... (Review)
Review
Vitamin K (VK), a fat-soluble vitamin, is essential for the clotting of blood because of its role in the production of clotting factors in the liver. Moreover, researchers continue to explore the role of VK as an emerging novel bioactive molecule with the potential function of improving bone health. This review focuses on the effects of VK on bone health and related mechanisms, covering VK research history, homologous analogs, dietary sources, bioavailability, recommended intake, and deficiency. The information summarized here could contribute to the basic and clinical research on VK as a natural dietary additive and drug candidate for bone health. Future research is needed to extend the dietary VK database and explore the pharmacological safety of VK and factors affecting VK bioavailability to provide more support for the bone health benefits of VK through more clinical trials.
Topics: Humans; Vitamin K; Vitamin K Deficiency; Bone and Bones; Blood Coagulation; Vitamins; Vitamin K 2; Vitamin K 1
PubMed: 38068793
DOI: 10.3390/nu15234935 -
Biochemical and Biophysical Research... Apr 1981
Topics: Chlorophyllides; Chloroplasts; Diterpenes; Phytol; Polyisoprenyl Phosphates
PubMed: 7247947
DOI: 10.1016/0006-291x(81)91249-3 -
Biochimica Et Biophysica Acta.... Mar 2017In vitro studies suggest that liver fatty acid binding protein (L-FABP) and sterol carrier protein-2/sterol carrier protein-x (SCP2/SCPx) gene products facilitate uptake...
In vitro studies suggest that liver fatty acid binding protein (L-FABP) and sterol carrier protein-2/sterol carrier protein-x (SCP2/SCPx) gene products facilitate uptake and metabolism and detoxification of dietary-derived phytol in mammals. However, concomitant upregulation of L-FABP in SCP2/SCPx null mice complicates interpretation of their physiological phenotype. Therefore, the impact of ablating both the L-FABP gene and SCP2/SCPx gene (L-FABP/SCP2/SCPx null or TKO) was examined in phytol-fed female wild-type (WT) and TKO mice. TKO increased hepatic total lipid accumulation, primarily phospholipid, by mechanisms involving increased hepatic levels of proteins in the phospholipid synthetic pathway. Concomitantly, TKO reduced expression of proteins in targeting fatty acids towards the triacylglycerol synthetic pathway. Increased hepatic lipid accumulation was not associated with any concomitant upregulation of membrane fatty acid transport/translocase proteins involved in fatty acid uptake (FATP2, FATP4, FATP5 or GOT) or cytosolic proteins involved in fatty acid intracellular targeting (ACBP). In addition, TKO exacerbated dietary phytol-induced whole body weight loss, especially lean tissue mass. Since individually ablating SCPx or SCP2/SCPx elicited concomitant upregulation of L-FABP, these findings with TKO mice help to resolve the contributions of SCP2/SCPx gene ablation on dietary phytol-induced whole body and hepatic lipid phenotype independent of concomitant upregulation of L-FABP.
Topics: Animals; Carrier Proteins; Diet; Fatty Acid-Binding Proteins; Fatty Acids; Female; Lipid Metabolism; Lipids; Liver; Mice; Mice, Inbred C57BL; Mice, Knockout; Phospholipids; Phytol; Triglycerides; Up-Regulation
PubMed: 27940000
DOI: 10.1016/j.bbalip.2016.12.002 -
Nutrients Apr 2023Vitamin K occupies a unique and often obscured place among its fellow fat-soluble vitamins. Evidence is mounting, however, that vitamin K (VK) may play an important role... (Review)
Review
Vitamin K occupies a unique and often obscured place among its fellow fat-soluble vitamins. Evidence is mounting, however, that vitamin K (VK) may play an important role in the visual system apart from the hepatic carboxylation of hemostatic-related proteins. However, to our knowledge, no review covering the topic has appeared in the medical literature. Recent studies have confirmed that matrix Gla protein (MGP), a vitamin K-dependent protein (VKDP), is essential for the regulation of intraocular pressure in mice. The PREDIMED (Prevención con Dieta Mediterránea) study, a randomized trial involving 5860 adults at risk for cardiovascular disease, demonstrated a 29% reduction in the risk of cataract surgery in participants with the highest tertile of dietary vitamin K1 (PK) intake compared with those with the lowest tertile. However, the specific requirements of the eye and visual system (EVS) for VK, and what might constitute an optimized VK status, is currently unknown and largely unexplored. It is, therefore, the intention of this narrative review to provide an introduction concerning VK and the visual system, review ocular VK biology, and provide some historical context for recent discoveries. Potential opportunities and gaps in current research efforts will be touched upon in the hope of raising awareness and encouraging continued VK-related investigations in this important and highly specialized sensory system.
Topics: Mice; Animals; Vitamin K; Vitamin K 1; Vitamins; Vitamin K Deficiency; Sense Organs; Vitamin K 2
PubMed: 37111170
DOI: 10.3390/nu15081948 -
Journal of Lipid Research Apr 2005Branched-chain fatty acids (such as phytanic and pristanic acid) are ligands for the nuclear hormone receptor peroxisome proliferator-activated receptor alpha...
Branched-chain fatty acids (such as phytanic and pristanic acid) are ligands for the nuclear hormone receptor peroxisome proliferator-activated receptor alpha (PPARalpha) in vitro. To investigate the effects of these physiological compounds in vivo, wild-type and PPARalpha-deficient (PPARalpha-/-) mice were fed a phytol-enriched diet. This resulted in increased plasma and liver levels of the phytol metabolites phytanic and pristanic acid. In wild-type mice, plasma fatty acid levels decreased after phytol feeding, whereas in PPARalpha-/- mice, the already elevated fatty acid levels increased. In addition, PPARalpha-/- mice were found to be carnitine deficient in both plasma and liver. Dietary phytol increased liver free carnitine in wild-type animals but not in PPARalpha-/- mice. Investigation of carnitine biosynthesis revealed that PPARalpha is likely involved in the regulation of carnitine homeostasis. Furthermore, phytol feeding resulted in a PPARalpha-dependent induction of various peroxisomal and mitochondrial beta-oxidation enzymes. In addition, a PPARalpha-independent induction of catalase, phytanoyl-CoA hydroxylase, carnitine octanoyltransferase, peroxisomal 3-ketoacyl-CoA thiolase, and straight-chain acyl-CoA oxidase was observed. In conclusion, branched-chain fatty acids are physiologically relevant ligands of PPARalpha in mice. These findings are especially relevant for disorders in which branched-chain fatty acids accumulate, such as Refsum disease and peroxisome biogenesis disorders.
Topics: Animals; Carnitine; Diet; Fatty Acids; Gene Deletion; Liver; Mice; Mice, Knockout; Mitochondria, Liver; Oxidation-Reduction; PPAR alpha; Peroxisomes; Phytol; Signal Transduction
PubMed: 15654129
DOI: 10.1194/jlr.M400337-JLR200 -
Bioscience, Biotechnology, and... 2013α-Amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) plays a key role in the regulation of NAD biosynthesis or the production of quinolinate from tryptophan...
α-Amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) plays a key role in the regulation of NAD biosynthesis or the production of quinolinate from tryptophan (Trp). We investigated in this study the effect of phytol, a phytochemical known as a peroxisome proliferator-activated receptor α (PPARα) ligand, on NAD synthesis and ACMSD expression in rats. Male Sprague-Dawley rats were fed a diet containing 0.5%, 1%, or 2% phytol for 7 d. Phytol decreased the ACMSD activity and its mRNA expression in a dose-dependent manner in the liver. Phytol similarly and significantly suppressed ACMSD mRNA expression in primary rat hepatocytes. However, the mRNA expression of ACO (a known PPARα target gene) was higher in the low-phytol groups than in the high-phytol group in vivo and in vitro. Phytol increased the blood NAD level by suppressing ACMSD mRNA expression in the liver of the rats. It is possible that this mechanism occurred by the activation of PPARα and also of other transcriptional factors.
Topics: Animals; Body Weight; Carboxy-Lyases; Diet; Eating; Gene Expression Regulation, Enzymologic; Hepatocytes; Male; NAD; Niacin; Organ Size; Phytol; Rats; Rats, Sprague-Dawley; Tryptophan
PubMed: 23832361
DOI: 10.1271/bbb.130029 -
Biochemical and Biophysical Research... Oct 2014Galactosylglycerolipids (GGLs) and chlorophyll are characteristic components of chloroplast in photosynthetic organisms. Although chlorophyll is anchored to the...
Galactosylglycerolipids (GGLs) and chlorophyll are characteristic components of chloroplast in photosynthetic organisms. Although chlorophyll is anchored to the thylakoid membrane by phytol (tetramethylhexadecenol), this isoprenoid alcohol has never been found as a constituent of GGLs. We here described a novel GGL, in which phytol was linked to the glycerol backbone via an ether linkage. This unique GGL was identified as an Alkaline-resistant and Endogalactosylceramidase (EGALC)-sensitive GlycoLipid (AEGL) in the marine green alga, Ulva pertusa. EGALC is an enzyme that is specific to the R-Galα/β1-6Galβ1-structure of galactolipids. The structure of U. pertusa AEGL was determined following its purification to 1-O-phytyl-3-O-Galα1-6Galβ1-sn-glycerol by mass spectrometric and nuclear magnetic resonance analyses. AEGLs were ubiquitously distributed in not only green, but also red and brown marine algae; however, they were rarely detected in terrestrial plants, eukaryotic phytoplankton, or cyanobacteria.
Topics: Cross-Linking Reagents; Ethers; Galactolipids; Phytol; Plant Extracts; Species Specificity; Ulva
PubMed: 25157808
DOI: 10.1016/j.bbrc.2014.08.056 -
Vitamins and Hormones 2008Vitamin K-dependent (VKD) protein carboxylation uses vitamin K epoxidation to convert Glus to carboxylated Glus (Glas), rendering VKD proteins active in physiologies... (Review)
Review
Vitamin K-dependent (VKD) protein carboxylation uses vitamin K epoxidation to convert Glus to carboxylated Glus (Glas), rendering VKD proteins active in physiologies that include hemostasis, apoptosis, bone mineralization, calcium homeostasis, growth control, and signal transduction. Clusters of Glus are modified by a processive carboxylase, generating a calcium-binding module that allows binding to either hydroxyapatite in the extracellular matrices or cell surfaces where anionic phospholipids become exposed, for example, during apoptosis or cell activation. Naturally occurring carboxylase mutations have been informative for function and are associated with bleeding complications and, surprisingly, a pseudoxanthoma elasticum (PXE)-like phenotype. A major advance in defining carboxylase function is the identification of the base that initiates carboxylation, which raises interesting possibilities for how vitamin K epoxidation is regulated by Glu substrate and carboxylase membrane topology. Vitamin K oxidoreductase (VKOR), the target of warfarin, generates the reduced vitamin K cofactor used by the carboxylase. Oxidation of active site thiols during vitamin K reduction inactivates VKOR, and activity is regenerated by an unknown reductase. The amounts of reduced vitamin K limit the capacity for carboxylation in cells, and overexpression of VKOR, but not carboxylase, improves carboxylation. However, the effect of VKOR overexpression is small, possibly because the reductase that regenerates VKOR activity is saturated. The review discusses these advances, as well as the potential impact of secretory components on carboxylation, which occurs during VKD protein secretion. Also discussed is the role of the carboxylase in mammals and lower organisms, including the bacterial pathogen Leptospira interrogans that has acquired a VKD carboxylase by horizontal transfer.
Topics: Animals; Carbon-Carbon Ligases; Cells, Cultured; Humans; NAD(P)H Dehydrogenase (Quinone); Oxidation-Reduction; Vitamin K; Vitamin K 1
PubMed: 18374193
DOI: 10.1016/S0083-6729(07)00007-6 -
International Journal of Molecular... Oct 1999The exposure of human lymphoid leukemia Molt 4B cells to phytol which was isolated from Lolium multiflorum Lam and identified by MS, and 1H- and 13C-NMR, led to both...
The exposure of human lymphoid leukemia Molt 4B cells to phytol which was isolated from Lolium multiflorum Lam and identified by MS, and 1H- and 13C-NMR, led to both growth inhibition and the induction of programmed cell death (apoptosis). Morphological change showing apoptotic bodies was observed in the cells treated with phytol. The fragmentation by phytol of DNA to oligonucleosomal-sized fragments that are characteristics of apoptosis was observed to be concentration- and time-dependent. These findings suggest that growth inhibition by phytol of Molt 4B cells results from the induction of apoptosis in the cells.
Topics: Apoptosis; DNA Fragmentation; Humans; Leukemia, Lymphoid; Lolium; Phytol; Tumor Cells, Cultured
PubMed: 10493978
DOI: 10.3892/ijmm.4.4.377