Synthesis and analysis of novel glycerolipids for the treatment of metabolic syndrome

Research output: Contribution to journalArticle

  • External authors:
  • Michael R. Jorgensen
  • Yushma Bhurruth-Alcor
  • Therese Røst
  • Pavol Bohov
  • Melanie Müller
  • Cristina Guisado
  • Endre Dyrøy
  • Rolf K. Berge
  • Andrew D. Miller
  • Jon Skorve

Abstract

Tetradecylthioacetic acid (TTA) 1 is a peroxisome proliferator-activated receptor (PPAR) agonist found to improve insulin sensitivity, lower blood lipid levels, enhance fatty acid oxidation, and promote anti-inflammation in vivo. In an attempt to enhance these properties, two key thioether fatty acid (Thefa) lipids, ditetradecylthioacetyl phosphatidylcholine 2 and tritetradecylthioacetyl glycerol 3, are synthesized and administered po to male Wistar rats at two different doses to study and compare metabolic outcomes relative to the administration of 1 alone after 6 days. Liposomal formulations of 1 and 2 are also prepared to evaluate acute metabolic responses (at 3 h) post iv injection. Across all metrics measured, 1-induced responses post po administration are in line with previous data. Responses induced from 3 are mostly equivalent to 1-induced responses. By contrast, 2-induced responses almost always outperform those of 1 and 3. Therefore, 2 may represent a new lead for the treatment of metabolic syndrome. © 2009 American Chemical Society.

Bibliographical metadata

Original languageEnglish
Pages (from-to)1172-1179
Number of pages7
JournalJournal of Medicinal Chemistry
Volume52
Issue number4
DOIs
Publication statusPublished - 26 Feb 2009