*Ingredient Spotlight from Apeiron's Nutrigenomic Lean*
Tetradecyl Thioacetic Acid ... What it is?
It is saturated, 16 carbon 3-thia synthetic, structurally modified, non-beta-oxidizable, omega-3 fatty acid.
It shows an enhanced potency in modulating critical steps in lipid metabolism
It has a sulfur atom inserted between the second and the third carbon counted from the carboxyl acid end, and because of this addition it cannot be burnt for energy and thus has no relevant caloric value to humans.
CH3-(CH2)13-S-CH2-COOH
How TTA is prepared:
TTA is not a natural occurring fatty acid, but is produced chemically from a Sulphur containing acid and potassium hydroxide dissolved in methanol. Tetraadcylbromide, which is the molecule basis for the TTA is added to the solution and through heating and pH regulation, the necessary reactions, will produce the TTA.
TTA is a dry, white crystalline product that is offered commercially.
Mechanism of action:
After administration to rats, 3-thia fatty acids have been shown to cause production of megaperoxisomes and micromitochondria , and stimulate the peroxisomal and mitochondrial b-oxidation of fatty acids. Although the 3-thia fatty acids are not b-oxidized, they can be catabolized by sulfur and w-oxidation to dicarboxylic acids that are subsequently excreted by the kidneys.
TTA is metabolized as an ordinary fatty acid and is incorporated into different lipid classes, especially into phospholipid
TTA acts as agonist at all subtypes of PPAR
A main determinant of the mechanism of action is the non-β-oxidizable nature of TTA.
Peroxisome proliferator activated receptors (PPARs):
They are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors, that play an important role in many cellular functions including lipid metabolism, cell proliferation, differentiation, adipogenesis and inflammatory signaling.
There are three distinct PPAR subtypes
PPARα is expressed in tissues exhibiting high rates of β-oxidation such as liver, kidney, heart and muscle. PPARα activation induces hepatomegaly and proliferation of liver peroxisomes. PPARα agonists (fibrates) have shown therapeutic utility as lipid lowering agents. (In simple words, PPARa tends to clear fats from the blood into muscle or liver cells, and encourage them to be burnt for energy in these locations)
PPARδ (also known as PPARβ and NUC1) is ubiquitously expressed in tissues and has been implicated in energy metabolism in both adipose and skeletal muscle.
PPARγ is highly expressed in adipose tissue and is a key transcription factor involved in the terminal differentiation of white and brown adipose tissue. PPARγ agonists such as the glitazones (thiazolidinediones) are marketed as antidiabetic agents. (PPARy makes new fat cells for fats to reside in which minimizes their potential toxicity).
There is evidence that both PPARα and PPARγ could interfere with atherogenesis, in part by exerting an anti-inflammatory activity.
|
Name |
PPARα |
PPARδ |
PPARγ |
|
Tissue expression |
Liver Kidney Heart Muscle |
Placenta |
Adipose tissue |
|
Physiological effects |
Fatty acid synthesis |
Fatty acid oxidation |
Adipocyte differentiation |
|
Disease relevance |
Dyslipidaemia |
Metabolic syndrome |
Diabetes |
Actions of TTA:
The biological responses to TTA include
- mitochondrial proliferation in liver, muscles and heart[1]
- increased catabolism of fatty acids,
- anti-adiposity, [2]
- improvement in insulin sensitivity[3]
- antioxidant properties [4]
- reduced proliferation and induction of apoptosis in rapidly proliferating cells [5]
- cell differentiation
- Anti-inflammatory action.
Role of TTA in Weight loss:
Attenuates Dyslipidemia (reduce plasma lipids level): due to increased mitochondrial fatty acid oxidation that is caused by activation of PPAR alpha and delta receptors.[6]
Several enzymes involved in lipid metabolism are induced after TTA treatment, including carnitine acetyltransferase and palmitoyl-CoA hydrolase, palmitoyl-CoA synthetase, acyl- CoA hydrolase etc.
Stimulation of PPAR-Alpha induce satiety and decrease appetite. This results in decrease oral intake and consequently helps in weight loss.[7]
It has a hypophagic effect which further helps in regulating obesity [8]
Furthermore, activators of PPARγ may increase feed intake and weight gain besides their beneficial effects on plasma lipids and insulin resistance.
TTA feeding promote reduced body weight gain in rats given high-fat diets, in spite of higher feed intake due to increased expression of UCP1 and UCP3.[9]
TTA reduced the total plasma cholesterol and triacylglycerol levels by 17% by increasing the number of mitochondria and by stimulating the mitochondrial β-oxidation of normal fatty acids
Summary of related studies:
|
Title |
Year |
Results |
DOI |
|
Tetradecylthioacetic acid prevents high fat diet induced adiposity and insulin resistance |
2002 |
TTA reduced adiposity, hyperglycemia, and markedly improved insulin sensitivity as determined by the intravenous glucose tolerance test |
https://pubmed.ncbi.nlm.nih.gov/11971945/ |
|
Hepatic fatty acid metabolism as a determinant of plasma and liver triacylglycerol levels. Studies on tetradecylthioacetic and tetradecylthiopropionic acids |
1995 |
TTA did potently reduce plasma cholesterol levels in rats and dogs and raised the HDL/LDL ratio by 40% |
10.1111/j.1432-1033.1995.tb20193.x |
|
Tetradecylthioacetic acid attenuates dyslipidaemia in male patients with type 2 diabetes mellitus, possibly by dual PPAR-α/δ activation and increased mitochondrial fatty acid oxidation |
2009 |
Mean LDL cholesterol level declined from 4.2 to 3.7 mmol/l, accompanied by increased levels of the HDL apolipoproteins A1 and A2, and a decline in LDL/HDL ratio from 4.00 to 3.66 was see. Total fatty acid also declined. |
https://doi.org/10.1111/j.1463-1326.2008.00958.x |
|
The PPAR pan-agonist tetradecylthioacetic acid promotes redistribution of plasma cholesterol towards large HDL |
2020 |
TTA promoted a shift in the plasma lipoprotein fractions with an increase in larger HDL particles. |
10.1371/journal.pone.0229322 |
|
Tetradecylthioacetic acid (a 3-thia fatty acid) decreases triacylglycerol secretion in CaCo-2 cells |
1995 |
TTA absorbed and metabolized as efficiently as oleic acid, tetradecylthioacetic acid was incorporated into cell-associated triacylglycerol to the same extent as normal fatty acids (e.g., oleic acid and palmitic acid), the amount of triacylglycerol secreted from cells incubated with tetradecylthioacetic acid was 8 to 10 times lower than the amount secreted from cells incubated with palmitic acid and oleic acid, respectively |
https://pubmed.ncbi.nlm.nih.gov/7775865/ |
|
Tetradecylthioacetic acid increases fat metabolism and improves cardiac function in experimental heart failure |
2013 |
TTA decreased free fatty acid levels and had a protective effect on myocardium when given combined with high fat diet |
10.1007/s11745-012-3749-z |
|
Cardioprotective effect of the PPAR ligand tetradecylthioacetic acid in type 2 diabetic mice |
2011 |
TTA increased myocardial fatty acid (FA) oxidation and improved ischemic tolerance in diabetic mice |
10.1152/ajpheart.00357.2010 |
|
Prevention of hypertension and organ damage in 2-kidney, 1-clip rats by tetradecylthioacetic acid |
2006 |
TTA attenuated the development of hypertension, reduced established hypertension, and prevented the development of organ damage in 2K1C rats, |
10.1161/01.HYP.0000233018.60736.70 |
|
Dietary supplementation of tetradecylthioacetic acid increases feed intake but reduces body weight gain and adipose depot sizes in rats fed on high-fat diets |
2009 |
Rats fed on TTA gained less body weight than lard-fed rats and had markedly decreased subcutaneous, epididymal, perirenal and mesenteric adipose depots. |
10.1111/j.1463-1326.2009.01092.x |
|
Lipid-lowering effects of tetradecylthioacetic acid in antipsychotic-exposed, female rats: challenges with long-term treatment |
2012 |
TTA had a protective role in antipsychotic-induced dyslipidemia |
10.1371/journal.pone.0050853 |
|
Comparative effects of oxygen and sulfur-substituted fatty acids on serum lipids and mitochondrial and peroxisomal fatty acid oxidation in rat |
1992 |
TTA stimulated the mitochondrial fatty acid oxidation, decreased serum cholesterol and decreased serum triacylglycerol |
10.1016/0006-2952(92)90248-h |
|
Inhibition of rat lipoprotein oxidation after tetradecylthioacetic acid feeding |
2002 |
Oral administration of TTA inhibited lipoprotein oxidase and prevented atheroscelorosis |
10.1016/s0006-2952(01)00934-0 |
|
The hypocholesterolemic effect of sulfur-substituted fatty acid analogues in rats fed a high carbohydrate diet |
1993 |
TTA reduced the activity of acyl-CoA:cholesterol acyltransferase (ACAT) and resulted in reduced cholesterol synthesis |
10.1016/0005-2760(93)90159-7 |
|
Dual acting and pan-PPAR activators as potential anti-diabetic therapies |
2011 |
PPAR-α activator drugs decrease plasma triglycerides and increase HDL-cholesterol levels. PPAR-δ activators increase the capacity for fat oxidation in skeletal muscle. |
10.1007/978-3-642-17214-4_2 |
|
An immunomodulating fatty acid analogue targeting mitochondria exerts anti-atherosclerotic effect beyond plasma cholesterol-lowering activity in apoe(-/-) mice |
2013 |
TTA administration reduce triglyceride levels in plasma and liver. It reduce arachidonic acid and increase EPA level in the heart. |
10.1371/journal.pone.0081963 |
|
Lipid-lowering and anti-inflammatory effects of tetradecylthioacetic acid in HIV-infected patients on highly active antiretroviral therapy |
2004 |
TTA in combination with dietary intervention reduces total cholesterol, LDL cholesterol, triglycerides and LDL/HDL cholesterol in HIV infected ptients on HAART |
10.1111/j.1365-2362.2004.01410.x |
|
Differences in fat accumulation between immature male and female Atlantic salmon Salmo salar after dietary administration of tetradecylthioacetic acid |
2016 |
The fat content during the first spring after dietary TTA was lowered by a greater amount in females than in males, In second spring fat was reduced more in males |
10.1111/jfb.13113 |
|
In contrast with docosahexaenoic acid, eicosapentaenoic acid and hypolipidaemic derivatives decrease hepatic synthesis and secretion of triacylglycerol by decreased diacylglycerol acyltransferase activity and stimulation of fatty acid oxidation. |
1999 |
TTA decreased triacylglycerol formation caused by inhibition of diacylglycerol acyltransferase and decreased availability of fatty acids for triacylglycerol synthesis by increased mitochondrial beta-oxidation |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1220541/ |
|
The effect of tetradecylthioacetic acid (TTA) on body weight management in growing silver foxes (Vulpes vulpes) as a model for dogs (Canis familiaris) |
2018 |
High dose reduced intake while low dose TTA reduced serum TGA, LDL cholesterol in foxes |
https://nmbu.brage.unit.no/nmbu-xmlui/bitstream/handle/11250/2570197/Chen-2018.pdf?sequence=1&isAllowed=y |
References: