Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Journal of Lipid Research |
| Vol/bind | 43 |
| Udgave nummer | 5 |
| Sider (fra-til) | 742-50 |
| Antal sider | 8 |
| ISSN | 0022-2275 |
| Status | Udgivet - 2002 |
| Udgivet eksternt | Ja |
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I: Journal of Lipid Research, Bind 43, Nr. 5, 2002, s. 742-50.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Tetradecylthioacetic acid prevents high fat diet induced adiposity and insulin resistance.
AU - Madsen, Lise
AU - Guerre-Millo, Michéle
AU - Flindt, Esben N
AU - Berge, Kjetil
AU - Tronstad, Karl Johan
AU - Bergene, Elin
AU - Sebokova, Elena
AU - Rustan, Arild C
AU - Jensen, Jørgen
AU - Mandrup, Susanne
AU - Kristiansen, Karsten
AU - Klimes, Iwar
AU - Staels, Bart
AU - Berge, Rolf K
PY - 2002
Y1 - 2002
N2 - Tetradecylthioacetic acid (TTA) is a non-beta-oxidizable fatty acid analog, which potently regulates lipid homeostasis. Here we evaluate the ability of TTA to prevent diet-induced and genetically determined adiposity and insulin resistance. In Wistar rats fed a high fat diet, TTA administration completely prevented diet-induced insulin resistance and adiposity. In genetically obese Zucker (fa/fa) rats TTA treatment reduced the epididymal adipose tissue mass and improved insulin sensitivity. All three rodent peroxisome proliferator-activated receptor (PPAR) subtypes were activated by TTA in the ranking order PPARalpha > PPARdelta > PPARgamma. Expression of PPARgamma target genes in adipose tissue was unaffected by TTA treatment, whereas the hepatic expression of PPARalpha-responsive genes encoding enzymes involved in fatty acid uptake, transport, and oxidation was induced. This was accompanied by increased hepatic mitochondrial beta-oxidation and a decreased fatty acid/ketone body ratio in plasma. These findings indicate that PPARalpha-dependent mechanisms play a pivotal role, but additionally, the involvement of PPARalpha-independent pathways is conceivable. Taken together, our results suggest that a TTA-induced increase in hepatic fatty acid oxidation and ketogenesis drains fatty acids from blood and extrahepatic tissues and that this contributes significantly to the beneficial effects of TTA on fat mass accumulation and peripheral insulin sensitivity.
AB - Tetradecylthioacetic acid (TTA) is a non-beta-oxidizable fatty acid analog, which potently regulates lipid homeostasis. Here we evaluate the ability of TTA to prevent diet-induced and genetically determined adiposity and insulin resistance. In Wistar rats fed a high fat diet, TTA administration completely prevented diet-induced insulin resistance and adiposity. In genetically obese Zucker (fa/fa) rats TTA treatment reduced the epididymal adipose tissue mass and improved insulin sensitivity. All three rodent peroxisome proliferator-activated receptor (PPAR) subtypes were activated by TTA in the ranking order PPARalpha > PPARdelta > PPARgamma. Expression of PPARgamma target genes in adipose tissue was unaffected by TTA treatment, whereas the hepatic expression of PPARalpha-responsive genes encoding enzymes involved in fatty acid uptake, transport, and oxidation was induced. This was accompanied by increased hepatic mitochondrial beta-oxidation and a decreased fatty acid/ketone body ratio in plasma. These findings indicate that PPARalpha-dependent mechanisms play a pivotal role, but additionally, the involvement of PPARalpha-independent pathways is conceivable. Taken together, our results suggest that a TTA-induced increase in hepatic fatty acid oxidation and ketogenesis drains fatty acids from blood and extrahepatic tissues and that this contributes significantly to the beneficial effects of TTA on fat mass accumulation and peripheral insulin sensitivity.
M3 - Journal article
C2 - 11971945
SN - 0022-2275
VL - 43
SP - 742
EP - 750
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 5
ER -