Skeletal Effects of the Saturated 3-Thia Fatty Acid Tetradecylthioacetic Acid in Rats

Astrid Kamilla Stunes,Janne Elin Reseland,Reidar Fossmark,Unni Syversen,Irene Westbroek,Rolf Kristian Berge

doi:10.1155/2011/436358

Abstract

This study explores the skeletal effects of the peroxisome proliferator activated receptor (PPAR)pan agonist tetradecylthioacetic acid (TTA). Rats, without (Study I) and with ovariectomy (OVX) or sham operation (Study II), were given TTA or vehicle daily for 4 months. Bone markers in plasma, whole body and femoral bone mineral density and content (BMD and BMC), and body composition were examined. Histomorphometric and biomechanical analyses (Study I) and biomechanical and μCT analyses (Study II) of the femur were performed. Normal rats fed TTA had higher femoral BMD and increased total and cortical area in femur compared to controls. The ovariectomized groups had decreased BMD and impaired microarchitecture parameters compared to SHAM. However, the TTA OVX group maintained femoral BMC, trabecular thickness in the femoral head, and cortical volume in the femoral metaphysis as SHAM. TTA might increase BMD and exert a light preventive effect on estrogen-related bone loss in rats.

Highlights

Fatty acids are natural ligands for peroxisome proliferator activated receptors (PPAR) α, δ, and γ
This study explores the skeletal effects of the peroxisome proliferator activated receptor (PPAR)pan agonist tetradecylthioacetic acid (TTA)
Due to the different effects of PPARγ agonists and PPARα agonists on bone metabolism, we aimed to examine the skeletal effect of TTA administration in intact as well as in ovariectomized female rats

Summary

Introduction

Fatty acids are natural ligands for peroxisome proliferator activated receptors (PPAR) α, δ, and γ. Tetradecylthioacetic acid (TTA) is a saturated 16 carbon 3-thia synthetic fatty acid, which acts as a PPARpan agonist. Studies have shown multifaceted effects of TTA in rodents. It induces mitochondrial fatty acid β-oxidation and causes reduced plasma levels of free fatty acids (FFA) and triglycerides (TG) in addition to improved insulin response, anti-inflammatory action and lowered oxidative stress [1,2,3]. The responses are qualitatively similar to the effects of n-3 fatty acids, but TTA seems to have a greater biological potency. A main determinant of the mechanism of action seems to be the non-β-oxidizability of TTA due to the sulphur atom in the third position in the carbon chain [4]

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Results

Conclusion