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 i.v. 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.
|
Authors | Michael R Jorgensen, Yushma Bhurruth-Alcor, Therese Røst, Pavol Bohov, Melanie Müller, Cristina Guisado, Kostas Kostarelos, Endre Dyrøy, Rolf K Berge, Andrew D Miller, Jon Skorve |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 52
Issue 4
Pg. 1172-9
(Feb 26 2009)
ISSN: 1520-4804 [Electronic] United States |
PMID | 19175322
(Publication Type: Journal Article)
|
Chemical References |
- Glycerides
- Peroxisome Proliferator-Activated Receptors
- Phosphatidylcholines
- Sulfides
- 1-(carboxymethylthio)tetradecane
- Glycerol
|
Topics |
- Animals
- Glycerides
(chemistry, pharmacology)
- Glycerol
- Male
- Metabolic Syndrome
(drug therapy)
- Peroxisome Proliferator-Activated Receptors
(agonists)
- Phosphatidylcholines
- Rats
- Rats, Wistar
- Sulfides
(chemistry, pharmacology)
|