Antiinflammatory Effects of Tetradecylthioacetic Acid Involve Both Peroxisome Proliferator–Activated Receptor α–Dependent and –Independent Pathways

Abstract

We show that TTA has the ability to attenuate tumor necrosis factor alpha-mediated endothelial cell activation, further supporting antiinflammatory effects of this fatty acid, possibly involving both PPAR-alpha-dependent and -independent pathways.

Peroxisome proliferator-activated receptors and acute lung injury

“…Moreover, the suppressive effect of PPAR-α ligands is mediated by inhibition of NF-κB activation, in part by enhancing the expression of IκBα [31]. It is important to note that synthetic and natural PPAR-α agonists can exert multiple biologic effects, including some which occur in a 4 PPAR Research PPAR-α-independent fashion [32]. WY14643, like GW7647, shows excellent selectivity for murine and human PPAR-α.…”

Fish oil and 3-thia fatty acid have additive effects on lipid metabolism but antagonistic effects on oxidative damage when fed to rats for 50 weeks

“…It thereby reduces the availability of fatty acids for very-low-density-lipoprotein synthesis and secretion and lowers plasma TAG and cholesterol levels. In addition, TTA has been shown to have an important role in diminishing of inflammation [12][13][14][15][16].…”

Tetradecylthioacetic acid downregulates cyclooxygenase 2 in the renal cortex of two-kidney, one-clip hypertensive rats

“…This clearly warrants further study. TTA exerts various effects via PPAR-dependent and -independent pathways (3,14). The blood pressure-lowering effect of other PPAR-activating drugs, such as the PPAR␥ ligand thiazolidinedione, as reviewed previously (9,13,42), is linked to renin expression, as we and others have shown previously (16,44).…”

“…For example, in COX2-deficient mice, the plasma renin level is low with reduced response to acute stimulation (25). In addition, there are studies that have shown a reduction of blood pressure (BP) after treatment with COX2 blockers in both 2K1C hypertension and inducible ANG II-dependent malignant hypertension in CYP1A-Ren2 transgenic rats (35, 56), although other reports show no effect on BP after COX2 inhibition as shown in a recent study by Richter et al (41).Tetradecylthioacetic acid (TTA) is a modified fatty acid that cannot undergo ␤-oxidation (2), and it is known to exert its various effects (4) by peroxisome proliferator-activated receptor (PPAR)-dependent or -independent pathways (3,14). We have recently shown that TTA prevents the development of hypertension in 2K1C by reducing the activation of the renin-angiotensin system (5, 16) and, furthermore, that TTA has a strong anti-inflammatory effect (6).…”

“…Tetradecylthioacetic acid (TTA) is a modified fatty acid that cannot undergo ␤-oxidation (2), and it is known to exert its various effects (4) by peroxisome proliferator-activated receptor (PPAR)-dependent or -independent pathways (3,14). We have recently shown that TTA prevents the development of hypertension in 2K1C by reducing the activation of the renin-angiotensin system (5,16) and, furthermore, that TTA has a strong anti-inflammatory effect (6).…”