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

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 two different doses to study and compare metabolic outcomes relative to the administration of 1 alone after 6 days. Liposomal formualtions of 1 and 2 are also prepared to evaluate responses post 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 theose of 1 and 3. Therefore, 2 may represent a new lead for the treatment of metabolic syndrome.