Phytanic acid, a natural peroxisome proliferator‐activated receptor agonist, regulates glucose metabolism in rat primary hepatocytes

• Published in: The FASEB journal 2002-05, Vol.16 (7), p.718-720
• Main Authors: Heim, Manuel, Johnson, James, Boess, Franziska, Bendik, Igor, Weber, Peter, Hunziker, Willi, Flühmann, Beat
• Format: Article
• Language: English
• Subjects: adipocyte; Adipocytes - cytology; Adipocytes - drug effects; Animals; Biological Transport - drug effects; Cell Differentiation; Cell Line; Cells, Cultured; glucokinase; Glucose - metabolism; glucose transporter; Hepatocytes - drug effects; Hepatocytes - metabolism; Hypoglycemic Agents - pharmacology; insulin resistance; Models, Biological; Phytanic Acid - pharmacology; phytol; Protein Isoforms - agonists; Rats; Receptors, Cytoplasmic and Nuclear - agonists; RNA, Messenger - biosynthesis; Transcription Factors - agonists; Transcriptional Activation
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.01-0816fje

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) α. PPAR agonists are widely used in the treatment of type 2 diabetes. Here, we report that phytanic acid is not only a transactivator of PPARα, but it also acts via PPARβ and PPARγ 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 PPARγ‐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.