title: Phytanic acid, a natural peroxisome proliferator-activated receptor (PPAR) agonist, regulates glucose metabolism in rat primary hepatocytes.
abstract: Phytanic acid, a metabolite of the chlorophyll molecule, is part of the human diet and is present in normal human serum at low micromolar concentrations. It was previously shown to be a ligand of the 9-cis-retinoic acid receptor and peroxisome proliferator-activated receptor (PPAR) a. PPAR agonists are widely used in the treatment of type 2 diabetes. Here, we report that phytanic acid is not only a transactivator of PPARa, but it also acts via PPARb and PPARg in CV-1 cells that have been cotransfected with the respective full-length receptor and an acyl-CoA oxidase-PPAR-responsive element-luciferase construct. We observed that, in contrast to other fatty acids, phytanic acid at physiological concentrations enhances uptake of 2-deoxy-D-glucose in rat primary hepatocytes. This result could be explained by the increase in mRNA expression of glucose transporters-1 and -2 and glucokinase, as determined by quantitative real-time reverse transcriptase-polymerase chain reaction. Compared with the PPARg-specific agonist ciglitazone, phytanic acid exerts only minor effects on the differentiation of C3H10T1/2 cells into mature adipocytes. These results clearly demonstrate that phytanic acid acts via different PPAR isoforms to modulate expression of genes involved in glucose metabolism, thus suggesting a potential role of phytanic acid in the management of insulin resistance.
authors.affiliation: Roche Vitamins Ltd, Research and Development, Department of Human Nutrition and Health, 4070 Basel, Switzerland.
authors.forename: Manuel
authors.initials: M
authors.lastname: Heim
authors.forename: James
authors.initials: J
authors.lastname: Johnson
authors.forename: Franziska
authors.initials: F
authors.lastname: Boess
authors.forename: Igor
authors.initials: I
authors.lastname: Bendik
authors.forename: Peter
authors.initials: P
authors.lastname: Weber
authors.forename: Willi
authors.initials: W
authors.lastname: Hunziker
authors.forename: Beat
authors.initials: B
authors.lastname: Fluhmann
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008954:Models, Biological; D010831:Phytanic Acid / Q000494:pharmacology*; D020033:Protein Isoforms / Q000819:agonists; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D014157:Transcription Factors / Q000819:agonists*; D015533:Transcriptional Activation
chemical_list: D007004:Hypoglycemic Agents; D020033:Protein Isoforms; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D010831:Phytanic Acid; D005947:Glucose