Modulation of rat liver apolipoprotein gene expression and serum lipid levels by tetradecylthioacetic acid (TTA) via PPARα activation

Abstract

3-Thia fatty acids are modified fatty acids that promote hepatic peroxisome proliferation and decrease serum triacylglycerol, cholesterol and free fatty acid levels in rats. In vivo administration of tetradecylthioacetic acid (TTA) to rats led to a significant decrease in liver apolipoproteins apoA-I, A-II, A-IV, and C-III mRNA levels, and to an increase of liver acyl-CoA oxidase (ACO), carnitine palmitoyltransferase-II, and 3-hydroxy-3-methylglutaryl coenzyme A synthase (HMG-CoA synthase) mRNA levels and activities. By contrast, no significant changes of lipoprotein lipase (LPL) mRNA levels were detected in rat epididymal adipose tissue. Liver carnitine palmitoyltransferase-I, apoB, apoE, and LDL receptor mRNA levels were not significantly affected. When tested in vitro, TTA increased rat ACO and carnitine palmitoyltransferase-I mRNA levels in primary rat hepatocytes and also LPL mRNA levels in 3T3-L1 preadipocytes. TTA also enhanced the transcriptional activity of chimeras containing the DNA binding domain of the yeast transcription factor Gal4 fused to the ligand binding domain of either human PPARα or human PPARγ. The effect depended on the concentration tested and the cell type. In conclusion, our data suggest that in vitro, TTA activates both PPARα and PPARγ, but the latter with much lower affinity. TTA affects serum lipid levels in vivo in rats by acting mainly on the liver via PPARα where it decreases the liver expression of genes involved in vascular lipid transport and increases the expression of genes involved in intracellular fatty acid metabolism.—Raspé, E., L. Madsen, A-M. Lefebvre, I. Leitersdorf, L. Gelman, J. Peinado-Onsurbe, J. Dallongeville, J-C. Fruchart, R. Berge, and B. Staels. Modulation of rat liver apolipoprotein gene expression and serum lipid levels by tetradecylthioacetic acid (TTA) via PPARα activation. J. Lipid Res. 1999. 40: 2099–2110. 3-Thia fatty acids are modified fatty acids that promote hepatic peroxisome proliferation and decrease serum triacylglycerol, cholesterol and free fatty acid levels in rats. In vivo administration of tetradecylthioacetic acid (TTA) to rats led to a significant decrease in liver apolipoproteins apoA-I, A-II, A-IV, and C-III mRNA levels, and to an increase of liver acyl-CoA oxidase (ACO), carnitine palmitoyltransferase-II, and 3-hydroxy-3-methylglutaryl coenzyme A synthase (HMG-CoA synthase) mRNA levels and activities. By contrast, no significant changes of lipoprotein lipase (LPL) mRNA levels were detected in rat epididymal adipose tissue. Liver carnitine palmitoyltransferase-I, apoB, apoE, and LDL receptor mRNA levels were not significantly affected. When tested in vitro, TTA increased rat ACO and carnitine palmitoyltransferase-I mRNA levels in primary rat hepatocytes and also LPL mRNA levels in 3T3-L1 preadipocytes. TTA also enhanced the transcriptional activity of chimeras containing the DNA binding domain of the yeast transcription factor Gal4 fused to the ligand binding domain of either human PPARα or human PPARγ. The effect depended on the concentration tested and the cell type. In conclusion, our data suggest that in vitro, TTA activates both PPARα and PPARγ, but the latter with much lower affinity. TTA affects serum lipid levels in vivo in rats by acting mainly on the liver via PPARα where it decreases the liver expression of genes involved in vascular lipid transport and increases the expression of genes involved in intracellular fatty acid metabolism.—Raspé, E., L. Madsen, A-M. Lefebvre, I. Leitersdorf, L. Gelman, J. Peinado-Onsurbe, J. Dallongeville, J-C. Fruchart, R. Berge, and B. Staels. Modulation of rat liver apolipoprotein gene expression and serum lipid levels by tetradecylthioacetic acid (TTA) via PPARα activation. J. Lipid Res. 1999. 40: 2099–2110. A group of modified fatty acids, in which a sulfur atom replaces a methylene group in a defined position of the carbon chain of an ordinary fatty acid (n-thia fatty acid), has been developed and extensively tested as hypolipidemic drugs (1Berge R.K. Hvattum E. Impact of cytochrome P450 system on lipoprotein metabolism. Effect of abnormal fatty acids (3-thia fatty acids).Pharmacol. Ther. 1994; 61: 345-383Google Scholar). 3-Thia fatty acids such as tetradecylthioacetic acid or TTA, a saturated fatty acid where the 3 methylene group is substituted (CH3-(CH2)13-S-CH2-COOH), are non-β oxidizable but can undergo ω-oxidation (1Berge R.K. Hvattum E. Impact of cytochrome P450 system on lipoprotein metabolism. Effect of abnormal fatty acids (3-thia fatty acids).Pharmacol. Ther. 1994; 61: 345-383Google Scholar). The other n-thia fatty acids can be metabolized both through β- or ω-oxidation and have different biological activities (1Berge R.K. Hvattum E. Impact of cytochrome P450 system on lipoprotein metabolism. Effect of abnormal fatty acids (3-thia fatty acids).Pharmacol. Ther. 1994; 61: 345-383Google Scholar). When administered to rats, 4-thia fatty acids promote fatty liver development and increase plasma triacylglycerol concentrations most probably through inhibition of fatty acid oxidation, whereas 3-thia fatty acids promote hepatic peroxisome and mitochondria proliferation and decrease serum triacylglycerol, cholesterol and free fatty acid levels (2Aarsland A. Berge R. Peroxisome proliferating sulphur-and oxysubstituted fatty acid analogues are activated to acyl coenzyme A thioesters.Biochem. Pharmacol. 1990; 41: 53-61Google A. Berge R.K. of fatty acids on rat hepatocytes with to proliferation of and 1990; J. A. A. Berge R.K. of fatty acid and and by hypolipidemic fatty acid Lipid Res. 1990; Scholar). triacylglycerol and has also been rats with TTA A. I. Berge R.K. fatty acid as a of plasma and liver triacylglycerol on tetradecylthioacetic and J. Scholar). In 3-thia fatty acids are to promote the expression and activity of acyl-CoA oxidase A. I. Berge R.K. fatty acid as a of plasma and liver triacylglycerol on tetradecylthioacetic and J. A. Hvattum E. J. Berge R.K. of hepatic fatty acyl-CoA oxidase and in rat of the peroxisome receptor by fatty acid 1994; carnitine L. A. Berge R.K. 3-hydroxy-3-methylglutaryl coenzyme A synthase and carnitine as and peroxisome Pharmacol. synthase L. A. Berge R.K. 3-hydroxy-3-methylglutaryl coenzyme A synthase and carnitine as and peroxisome Pharmacol. L. Berge R.K. 3-Thia fatty acids in to acid and gene expression of carnitine in rat L. Berge R.K. of genes and by 3-thia fatty Pharmacol. Scholar). fatty acids of chain but with a sulfur atom in the position of the chain the TTA effect L. A. Berge R.K. 3-hydroxy-3-methylglutaryl coenzyme A synthase and carnitine as and peroxisome Pharmacol. L. L. A. L. J. A. Berge R.K. Effect of 3-thia fatty acids on the lipid of rat and Lipid Res. Scholar). are of which are plasma lipid The of apolipoproteins in plasma lipoprotein were by the of or of of either the human apolipoprotein genes or in apolipoprotein genes by of lipoprotein The of I. of lipoprotein and Scholar). mainly the on apoA-I, and lipoprotein lipase in lipoprotein and triacylglycerol metabolism. is a of a lipoprotein involved in cholesterol transport and in of cholesterol to J-C. and in gene is in and Scholar). concentrations have been to be with plasma triacylglycerol levels, in and in J. J. and C-III levels in J. with an abnormal lipoprotein apolipoprotein of plasma apolipoprotein and C-III concentrations in and the of the of Lipid Res. as as in of the human gene A. A. as a of human gene expression in 1990; Scholar). of the gene by in led to plasma and triacylglycerol concentrations and the J. of the apolipoprotein C-III gene in in and 1994; Scholar). triacylglycerol levels are also by the activity of LPL I. lipase and in lipoprotein and Lipid Res. Scholar). LPL as is by and in and free fatty acids which are by the and LPL genes are genes hypolipidemic The of drugs in have been on lipoprotein B. J. J. E. J-C. The of of on lipid and lipoprotein Scholar). are most in plasma both in human and by gene expression B. R. J. J. apolipoprotein C-III expression of of acyl coenzyme A Scholar). In apoA-I, and gene expression in and plasma cholesterol levels B. A. J. the expression of genes involved in lipoprotein in a in the B. A. J. acid is in a 1990; L. R. J. B. of rat liver apolipoprotein apolipoprotein A-II, and A oxidase gene expression by and fatty J. Scholar). but not or gene expression and LDL receptor gene expression B. A. J. the expression of genes involved in lipoprotein in a in the Scholar). mRNA levels are also by but not by or of of rats but to levels 3 of B. A. J. the expression of genes involved in lipoprotein in a in the Scholar). the expression of LPL in the liver of rats, with no effect on adipose J. A-M. B. J. PPARα and a transcriptional via a in the lipoprotein lipase J. Scholar). have been to be and of of the peroxisome receptor receptor E. acids, and hypolipidemic as of peroxisome by receptor ligand J. fatty acids, and are peroxisome and Scholar). different of or and have been in by a different gene and expression B. J. of in the of lipoprotein by and Scholar). ligand and to the acid receptor of acid and peroxisome through of J. A. acids and lipid through of peroxisome receptor to peroxisome in the of genes B. J. of in the of lipoprotein by and Scholar). In to the acid or have been as PPARα E. acids, and hypolipidemic as of peroxisome by receptor ligand The to whereas the as the and the acid have been to be I. A peroxisome receptor and is a ligand peroxisome receptor J. is a ligand the factor Scholar). have been in the of genes involved in such as the human R. J. J. of of peroxisome as hypolipidemic of apolipoprotein and the and human LPL genes J. A-M. B. J. PPARα and a transcriptional via a in the lipoprotein lipase J. as as in plasma such as the human B. J. B. of the human apolipoprotein by can be by the of the peroxisome receptor with 1994; and J. J-C. B. J. increase human apolipoprotein expression through of the peroxisome the of on the expression of genes in where the PPARα gene is by B. J-C. J. in lipoprotein in Scholar). data that PPARα the of on apolipoprotein gene In to plasma lipid levels, also promote peroxisome proliferation in B. J. of in the of lipoprotein by and and The of peroxisome proliferation in the of receptor in the of peroxisome J. of the of the peroxisome receptor gene in in of the of peroxisome Scholar). By contrast, such as epididymal adipose LPL mRNA but not liver apolipoprotein or ACO gene expression A-M. J. I. J-C. J. B. of lipoprotein by through a but to Scholar). administration of and in a of serum that drugs with PPARα and activity an increased activity A-M. J. I. J-C. J. B. of lipoprotein by through a but to Scholar). fatty acids are PPARα and E. acids, and hypolipidemic as of peroxisome by receptor ligand J. fatty acids, and are peroxisome and 3-thia fatty acids are such The of to 3-thia fatty acids by the expression of genes involved in lipid transport and lipoprotein in hepatic and adipose in to the hypolipidemic of 3-thia fatty acids be with of PPARα in acid (TTA) as J. of in in by fatty acids and fatty acid Scholar). and acid were and A. acid The lipid a rats were in and a of The were the of the and with to TTA in and administered by a a of The free to and the of the the rats were and by in by Liver and epididymal were and in as in the the and of lipid concentrations and free were of of serum rats were on a and a of with The in and cholesterol and triacylglycerol concentrations were in of hepatocytes were by L. R. J. B. of rat liver apolipoprotein apolipoprotein A-II, and A oxidase gene expression by and fatty J. of rats of and When cell by the the were in and as a in a of The with serum by fatty a in and were in or and to the by the were with and in of 3T3-L1 were as J. A-M. B. J. PPARα and a transcriptional via a in the lipoprotein lipase J. and the in the of tetradecylthioacetic the of the were with and in of were were in modified with serum in a of The rats were in and and were as R.K. of acyl-CoA activity in and mitochondria of rat liver by J. Scholar). The of the by the the in as acyl-CoA oxidase activity in the as A. I. Berge R.K. fatty acid as a of plasma and liver triacylglycerol on tetradecylthioacetic and J. Scholar). were as J. Berge R.K. acid no but increases the fatty acid in liver of Lipid Res. Scholar). the and with with the with and were The were and of the and activity as by J. The effect of on the activity of liver carnitine and inhibition by Scholar). The and The with were that and concentration synthase to of the 3-hydroxy-3-methylglutaryl in the Scholar). liver and epididymal adipose or cell by the acid of by acid Scholar). and of were as B. A. J. the expression of genes involved in lipoprotein in a in the Scholar). apoA-I, apoE, apoB, LDL acyl-CoA oxidase (ACO), and human LPL were as B. R. J. J. apolipoprotein C-III expression of of acyl coenzyme A B. A. J. the expression of genes involved in lipoprotein in a in the J. R. of the lipoprotein lipase and apolipoprotein genes in human cell Scholar). and of and and β- and genes and R. J. A. of of genes human cell Res. the human J. as an mRNA is the human Res. were as A of of rat the to of the rat mRNA and expression of a rat liver carnitine by as J. R. A. expression of and fatty acid in rat J. 1994; Scholar). A rat A. and expression of a rat liver carnitine 1990; a to the of the rat which been in J. and are by different 1990; were as were by were to of as B. A. J. the expression of genes involved in lipoprotein in a in the Scholar). were in and and and to were by as B. A. J. the expression of genes involved in lipoprotein in a in the Scholar). The by of a of the of the the B. with the of and Res. as and the and by of the with and and the of the The by of the Gal4 DNA binding J. The yeast is a transcriptional in human in the of the in of the of the The as by the yeast transcription factor Gal4 DNA binding domain in the the of the The by a of the L. E. A-M. R. J. J-C. A. J. B. J. The and expression of the human the of the and the the of the The the acids to of the Gal4 transcription factor and the acids to of The by the the J-C. J. E. B. A human peroxisome receptor with as with the the in the of and the the of the The the acids to of the Gal4 transcription factor and the acids to of were by were in a of or or 3T3-L1 and to were in serum the lipid The and of the cell of DNA were in both cell The which the expression of the gene the of the as of whereas the as DNA to the of DNA to The and and were in with and the lipid and to the were with and in containing serum and the tested or by the of the the were with and the activity with the to the were 3 of the by the the were by to the or the where is the concentration of A the and and are by a on a a with the and the were to the In a of rats were with TTA a to peroxisome proliferation and to decrease plasma lipid levels plasma lipid levels and apolipoprotein and LPL gene expression were TTA significantly increased liver significantly the or the not A significant decrease in serum and cholesterol acid effect are to A. I. Berge R.K. fatty acid as a of plasma and liver triacylglycerol on tetradecylthioacetic and J. the effect of TTA on the lipoprotein of TTA on rat liver and ACO and serum were rats with TTA or acid the in and levels were by Liver ACO activity as A. I. Berge R.K. fatty acid as a of plasma and liver triacylglycerol on tetradecylthioacetic and J. Scholar). oxidation, and activities were as A. I. Berge R.K. fatty acid as a of plasma and liver triacylglycerol on tetradecylthioacetic and J. J. The effect of on the activity of liver carnitine and inhibition by of the 3-hydroxy-3-methylglutaryl in the Scholar). in a Liver and serum were rats with TTA or acid the in and levels were by Liver ACO activity as A. I. Berge R.K. fatty acid as a of plasma and liver triacylglycerol on tetradecylthioacetic and J. Scholar). oxidation, and activities were as A. I. Berge R.K. fatty acid as a of plasma and liver triacylglycerol on tetradecylthioacetic and J. J. The effect of on the activity of liver carnitine and inhibition by of the 3-hydroxy-3-methylglutaryl in the Scholar). or were by and triacylglycerol and that the decrease of TTA is mainly in of rats with TTA decreases the cholesterol in both and and in TTA of rats by a increase of the ACO gene expression in to an increase in liver ACO activity A of apoA-I, and liver mRNA levels TTA whereas and mRNA levels were in acid liver mRNA levels were but by TTA in most of rats with TTA on in TTA whereas in as in a decrease the effect on other apolipoprotein In to liver apolipoprotein gene also liver and mRNA levels and activities were also modified by TTA in to data L. A. Berge R.K. 3-hydroxy-3-methylglutaryl coenzyme A synthase and carnitine as and peroxisome Pharmacol. that synthase and mRNA levels and activities where by TTA whereas mRNA in most of LPL gene expression in epididymal adipose not by TTA whereas it increased in the of TTA on rat epididymal adipose mRNA were rats with TTA or acid the in as A-M. J. I. J-C. J. B. of lipoprotein by through a but to Scholar). LPL or mRNA levels were by are in the as in a were rats with TTA or acid the in as A-M. J. I. J-C. J. B. of lipoprotein by through a but to Scholar). LPL or mRNA levels were by are in the as of both PPARα and to on plasma triacylglycerol levels A-M. J. I. J-C. J. B. of lipoprotein by through a but to and as the of TTA are to of the of TTA on PPARα and by with chimeras the domain of the yeast transcription factor Gal4 fused to the ligand binding domain of either human PPARα or and a containing of the Gal4 in of the and the gene as is a ligand peroxisome receptor Scholar). The of is that the is as the chimeras and the Gal4 transcription factor are not in When with the in the activated by the but not by the the not by either or By contrast, the by but by The of and were the are in TTA also activated the in a A significant a concentration as as The effect 3 but the effect of tested the other TTA a of the in a effect has to be to the of by tested a concentration of of by of the and chimeras in and 3T3-L1 of on and chimeras in and 3T3-L1 were as in and by a The are of in a of on and chimeras in and 3T3-L1 were as in and by a The are of When 3T3-L1 were with the and the expression an of activity also in to and TTA, whereas the other the mainly activated by and TTA tested concentrations and by the activity with The of were the are in When the of the and chimeras by and TTA are in the cell can be the and by TTA are but significantly lower in 3T3-L1 the of is lower in 3T3-L1 are by the of the and chimeras by TTA is in 3T3-L1 whereas the effect on the is the effect on the in to the effect of tested the of the by TTA tested is in 3T3-L1 in of the effect in 3T3-L1 in data suggest in and in the cell TTA can both PPARα and PPARγ. the of concentrations PPARα activation. TTA gene expression in of hepatic or adipose and the rat hepatocytes in primary or 3T3-L1 were with TTA and and with genes to be and as activation. The expression of the rat ACO which is by or other PPARα L. R. J. B. of rat liver apolipoprotein apolipoprotein A-II, and A oxidase gene expression by and fatty J. increased in a TTA of primary rat hepatocytes data suggest that TTA on the rat and activates In to in to fatty acid also be in by TTA, the of and of primary hepatocytes with A increase in mRNA A increase in mRNA also not the other a of LPL mRNA of 3T3-L1 with TTA a concentration which enhanced activity effect to the of A-M. J. I. J-C. J. B. of lipoprotein by through a but to Scholar). in vitro, TTA on the and in 3-Thia fatty acids are modified fatty acids that are to promote hepatic peroxisome proliferation and to decrease serum triacylglycerol, and free fatty acid levels administered to rats (1Berge R.K. Hvattum E. Impact of cytochrome P450 system on lipoprotein metabolism. Effect of abnormal fatty acids (3-thia fatty acids).Pharmacol. Ther. 1994; 61: 345-383Google Scholar). In to on plasma lipoprotein the of TTA, of the most 3-thia fatty acids, on liver apolipoprotein gene expression in rats with the a increase of ACO gene expression in liver with a of apoA-I, and liver gene as as the peroxisome proliferation of TTA, are to of B. J. of in the of lipoprotein by and our suggest that TTA of with The that TTA increases ACO gene expression not in vivo but also in in rat hepatocytes in primary that the of TTA on liver gene expression are in in rats, the of plasma cholesterol is in the expression of liver apolipoproteins A-II, and A-IV, which are of J-C. and in gene B. R. J. and in human an most to the effect of In to effect on apolipoprotein gene TTA also affects the liver activity of the in cholesterol A. I. Berge R.K. fatty acid as a of plasma and liver triacylglycerol on tetradecylthioacetic and J. Scholar). The decrease in plasma cholesterol probably on transport and of triacylglycerol levels on the triacylglycerol and by the liver as as on of is a of triacylglycerol by LPL by or I. lipase and in lipoprotein and Lipid Res. J. Scholar). are by which a in the of plasma triacylglycerol levels J. of human apolipoprotein C-III in in an of apolipoprotein that is by apolipoprotein 1994; R. A. R. of in human apolipoprotein lipoprotein with increased and on the Modulation of lipoprotein binding to the LDL receptor by and apolipoproteins and L. of the of human and C-III Lipid Res. R. to apolipoprotein in apolipoprotein is not by on apolipoprotein Scholar). liver or LDL receptor and adipose LPL gene are not significantly by TTA and as to the on other apolipoproteins are on gene expression in but not the in liver expression by TTA a of effect on triacylglycerol In to effect on triacylglycerol TTA has been to triacylglycerol and A. I. Berge R.K. fatty acid as a of plasma and liver triacylglycerol on tetradecylthioacetic and J. and to intracellular TTA the expression and activity of with increased peroxisome proliferation A. I. Berge R.K. fatty acid as a of plasma and liver triacylglycerol on tetradecylthioacetic and J. A. Hvattum E. J. Berge R.K. of hepatic fatty acyl-CoA oxidase and in rat of the peroxisome receptor by fatty acid 1994; Scholar). increased proliferation A. Berge R.K. of fatty acids on rat hepatocytes with to proliferation of and 1990; and fatty acid A. I. Berge R.K. fatty acid as a of plasma and liver triacylglycerol on tetradecylthioacetic and J. TTA of rats. chain fatty acid the transport of chain fatty acids the and via the and the is as the with TTA, but not to the increases the expression of L. A. Berge R.K. 3-hydroxy-3-methylglutaryl coenzyme A synthase and carnitine as and peroxisome Pharmacol. L. Berge R.K. of genes and by 3-thia fatty Pharmacol. Scholar). By contrast, the expression of the of is by with TTA L. A. Berge R.K. 3-hydroxy-3-methylglutaryl coenzyme A synthase and carnitine as and peroxisome Pharmacol. Scholar). The of expression in hepatocytes in primary but not in vivo in rats of with TTA is with data L. A. Berge R.K. 3-hydroxy-3-methylglutaryl coenzyme A synthase and carnitine as and peroxisome Pharmacol. L. Berge R.K. of genes and by 3-thia fatty Pharmacol. Scholar). our data that the TTA effect on expression is to a effect on the our on expression are also with data L. A. Berge R.K. 3-hydroxy-3-methylglutaryl coenzyme A synthase and carnitine as and peroxisome Pharmacol. L. Berge R.K. of genes and by 3-thia fatty Pharmacol. Scholar). by can be as a carbon the of synthase a in of hepatic fatty acid and Scholar). that the expression and the activity of are increased by TTA in rats L. A. Berge R.K. 3-hydroxy-3-methylglutaryl coenzyme A synthase and carnitine as and peroxisome Pharmacol. Scholar). The data in conclusion, TTA a of on transport and as as on intracellular and of to in a decrease of plasma triacylglycerol The of to the effect of TTA to be the of PPARα in the of on liver apolipoprotein gene expression is B. J. of in the of lipoprotein by and and as TTA has to of to TTA A of the by TTA in the effect of TTA is lower the of such as the TTA is lower that of increased that TTA be of The of ACO gene expression in primary rat hepatocytes L. R. J. B. of rat liver apolipoprotein apolipoprotein A-II, and A oxidase gene expression by and fatty J. an effect of which is on PPARα J. of the of the peroxisome receptor gene in in of the of peroxisome that TTA is also on the of PPARα by TTA has been in with an ACO and a PPARα expression J. fatty acids, and are peroxisome and Scholar). data that TTA on liver gene expression by In to PPARα TTA, as other fatty acids, also PPARγ, which in a activity A-M. J. I. J-C. J. B. of lipoprotein by through a but to Scholar). the of effect of TTA on epididymal adipose LPL expression in most of our with the effect of the on rat adipose A-M. J. I. J-C. J. B. of lipoprotein by through a but to and in vivo of in rats. that the liver is the TTA of in is by the of a of the of the effect of the are with TTA a to concentration the effect on the and by the of activity of TTA on activity in J. fatty acids, and are peroxisome and Scholar). In the of the by TTA in the effect of the on the a significant of the of the effect of the tested in cell 3T3-L1 cell a concentration the of the in and in to of both chimeras by TTA The by TTA of the expression of the gene LPL in 3T3-L1 that TTA is to the in The on the the in by TTA of the and the of LPL expression in 3T3-L1 on the other the of in by TTA of the in J. fatty acids, and are peroxisome and and the of in vivo effect of TTA on adipose LPL gene expression can not be to in with the of chimeras the and of is that the the of TTA is in adipose to PPARγ. TTA has been detected in adipose of rats but concentration in lower to hepatic concentration L. A. Berge R.K. effect of tetradecylthioacetic a on plasma lipid and fatty acid and in different rat Scholar). a concentration of where is in is of the effect of in 3T3-L1 In it is that the of by a ligand or is by the to of the in 3T3-L1 to in and by in by in different R. J. A. and ligand of peroxisome Scholar). cell in to be to cell in transport or of the in expression of which the to the transcription J. and in the of transcriptional The receptor and in expression levels have been and in different or cell L. and of and Scholar). that TTA other which be in rat adipose or 3T3-L1 and and which with TTA also activates tested in J. fatty acids, and are peroxisome and Scholar). In conclusion, the in suggest that the of the lipid of TTA, a 3-thia fatty is the liver where it the expression of apolipoproteins and involved in lipid transport and metabolism. of apolipoprotein gene expression in with the of the on intracellular and fatty acid the hypolipidemic effect of in data that TTA mainly activates tested a significant of be concentrations and in the cell our data suggest that the lipid of TTA in vivo in rats be to of both PPARα and PPARγ. our data that the of is on the The be cell the in vivo tissue. it be to with by and J. is by the The B. E. and also E. lipoprotein lipase peroxisome receptor peroxisome receptor acyl-CoA oxidase carnitine palmitoyltransferase-I carnitine 3-hydroxy-3-methylglutaryl coenzyme A synthase tetradecylthioacetic acid acid lipoprotein lipoprotein acid serum acid chain modified peroxisome receptor and receptor receptor