Anti-inflammatory and hypolipidemic effects of the modified fatty acid tetradecylthioacetic acid in psoriasis – a pilot study

Abstract

Tetradecylthioacetic acid (TTA) is a bioactive 3-thia fatty acid, giving hypolipidemic response, inhibiting the proliferation and increasing the differentiation of normal adult epidermal keratinocytes and showing anti-oxidant and anti-inflammatory effects. Psoriasis is an inflammatory disease associated with abnormalities in lipid profile, lipid peroxidation, antioxidant capacity, eicosanoid metabolism and increased frequency of cardiovascular events. On this background we have conducted a pilot study to explore the hypothesis that this modified fatty acid could improve dyslipidemia and reduce inflammation in psoriatic patients. In this double-blinded, placebo-controlled study, we assessed the metabolic effects of systemic TTA in a limited number of patients with mild to moderate psoriasis, 1000 mg TTA daily for 28 days. The most important findings were: (i) TTA reduced plasma total cholesterol, non HDL-cholesterol, LDL/HDL cholesterol ratio, triglycerides and total fatty acids; (ii) TTA decreased plasma TNF-α, IL-8 and VCAM-1; and (iii) plasma fatty acid composition changed with an increased level of monounsaturated fatty acids and decreased n-3 polyunsaturated fatty acids. In conclusion TTA exerts both hypolipidemic and anti-inflammatory effects in psoriasis patients. The results further indicate that TTA can be of therapeutic benefit for a subgroup of psoriatic patients.

AMP-activated protein kinase and ATP-citrate lyase are two distinct molecular targets for ETC-1002, a novel small molecule regulator of lipid and carbohydrate metabolism

“…ACC, acetyl-CoA carboxylase; ACS, acyl-CoA synthetase; ␤ -Ox, ␤ -oxidation; CPT-1, carnitine palmitoyltransferase-1; G6Pase, glucose 6-phosphatase; HMGR, HMG-CoA reductase; PEPCK, phosphoenolpyruvate carboxykinase; TCA, tricarboxylic acid. compounds (82)(83)(84)(85)(86)(87)(88)(89)(90)(91)(92) and provide further clarity into their respective mechanisms ( 84,91,(93)(94)(95)(96)(97)(98)(99)(100).…”

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

“…Recently, in a double-blinded, placebo-controlled study, we assessed the metabolic effects of systemic TTA in patients with mild to moderate psoriasis, 1.0 g TTA for 28 days [38]. The most important findings were that TTA reduced the plasma lipids (cholesterol, triglycerides, and total fatty acid) and showed anti-inflammatory effects as it lowered the plasma tumor necrosis factor- α and vascular cell adhesion molecule-1.…”

“…No significant adverse effects or other complications were reported throughout the study. All safety parameters remained within the normal limits both for males and females in the placebo and TTA group [38]. …”

An Immunomodulating Fatty Acid Analogue Targeting Mitochondria Exerts Anti-Atherosclerotic Effect beyond Plasma Cholesterol-Lowering Activity in apoE-/- Mice

“…Following cellular uptake, TTA is converted to TTA-CoA [6], which is a good substrate for the carnitine palmitoyltransferase system (CPT1 and CPT2) [7], transporting acyl-CoA into the mitochondria. However, due to the sulphur atom at the 3 position TTA is blocked for β-oxidation [8], and the S-substitution also contribute to the antioxidant effect [9]. TTA stimulates mitochondrial fatty acid oxidation of normal β-oxidizable fatty acids [10] and induces mitochondrial proliferation in rat hepatocytes [11].…”

“…As a pan-ligand for members of the peroxisome proliferator-activated receptor (PPAR) family of nuclear hormone receptors, TTA regulates expression of fatty acid metabolizing enzymes, in particular those of the catabolic pathway [12–14]. TTA is reported to have both cholesterol- and triacylglycerol (TAG) lowering effect in in psoriasis patients [8]. The increased mitochondrial fatty acid oxidation and mitochondrial proliferation seem to be important in regulating plasma TAG level [11,12].…”