Fatty acid flux suppresses fatty acid synthesis in hamster intestine independently of SREBP-1 expression

Hamsters were fed a control diet or diets containing palm, olive, safflower, or fish oil for 2 weeks. In villus cell populations from duodenum, jejunum, and ileum, rates of intestinal fatty acid and cholesterol synthesis were estimated, as were sterol regulatory element-binding protein (SREBP)-1a, SREBP-1c, SREBP-2, HMG-CoA synthase, fatty acid synthase, ATP citrate lyase, acetyl-CoA carboxylase mRNA levels, and SREBP-1 and SREBP-2 mass. Plasma cholesterol and triacylglcerol levels were increased in animals ingesting palm oil and decreased in animals ingesting fish oil. Fatty acid synthesis and fatty acid synthase activity were decreased in the proximal intestine of animals ingesting all the fat-containing diets. Intestinal cholesterol synthesis was unaltered. In animals fed fat, SREBP-1c gene expression was modestly increased in the duodenum of hamsters fed palm oil or olive oil, and decreased in animals ingesting safflower oil or fish oil. Fatty acid synthase, acetyl-CoA carboxylase, ATP citrate lyase, SREBP-2, and HMG-CoA synthase mRNA levels were not altered, nor were SREBP-1 or SREBP-2 mass. In the intestine, dietary polyunsaturated fatty acids suppress SREBP-1c mRNA without altering expression of its target genes, fatty acid synthase, acetyl-CoA carboxylase, or ATP citrate lyase.Fatty acid influx decreases intestinal fatty acid synthesis by a posttranscriptional mechanism independent of the SREBP pathway. Hamsters were fed a control diet or diets containing palm, olive, safflower, or fish oil for 2 weeks. In villus cell populations from duodenum, jejunum, and ileum, rates of intestinal fatty acid and cholesterol synthesis were estimated, as were sterol regulatory element-binding protein (SREBP)-1a, SREBP-1c, SREBP-2, HMG-CoA synthase, fatty acid synthase, ATP citrate lyase, acetyl-CoA carboxylase mRNA levels, and SREBP-1 and SREBP-2 mass. Plasma cholesterol and triacylglcerol levels were increased in animals ingesting palm oil and decreased in animals ingesting fish oil. Fatty acid synthesis and fatty acid synthase activity were decreased in the proximal intestine of animals ingesting all the fat-containing diets. Intestinal cholesterol synthesis was unaltered. In animals fed fat, SREBP-1c gene expression was modestly increased in the duodenum of hamsters fed palm oil or olive oil, and decreased in animals ingesting safflower oil or fish oil. Fatty acid synthase, acetyl-CoA carboxylase, ATP citrate lyase, SREBP-2, and HMG-CoA synthase mRNA levels were not altered, nor were SREBP-1 or SREBP-2 mass. In the intestine, dietary polyunsaturated fatty acids suppress SREBP-1c mRNA without altering expression of its target genes, fatty acid synthase, acetyl-CoA carboxylase, or ATP citrate lyase. Fatty acid influx decreases intestinal fatty acid synthesis by a posttranscriptional mechanism independent of the SREBP pathway. Sterol regulatory element-binding proteins (SREBPs) are transcription factors that regulate the transcription of several genes in both the cholesterol and fatty acid synthetic pathways [reviewed in ref. (1Brown M.S. Goldstein J.L. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor.Cell. 1997; 89: 331-340Google Scholar)]. SREBP-1a and SREBP-1c are derived from a single gene that uses an alternative transcriptional start site to produce the two isoforms of SREBP-1 (2Hua X. Wu J. Goldstein J.L. Brown M.S. Hobbs H.H. Structure of the human gene encoding sterol regulatory element binding protein-1 (SREBF1) and localization of SREBF1 and SREBF2 to chromosomes 17p11.2 and 22q13.Genomics. 1995; 25: 667-673Google Scholar). SREBP-2 is a product of a separate gene and has 50% homology to SREBP-1. All three SREBPs are synthesized as 125 kDa precursor proteins bound to the endoplasmic reticulum. In times of cholesterol deficiency, a two-step proteolysis of the precursor protein releases a 68 kDa N-terminal end of the protein producing the active transcription factor. This “mature” or nuclear form enters the nucleus and binds to a 10 bp sterol regulatory element in promoter regions of target genes that result in enhanced transcription (3Osborne T.F. Transcriptional control mechanisms in the regulation of cholesterol balance.Crit. Rev. Eukaryot. Gene Expr. 1995; 5: 317-335Google Scholar, 4Kim J.B. Spiegelman B.M. ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism.Genes Dev. 1996; 10: 1096-1107Google Scholar, 5Pak Y.K. Serum response element-like sequences of the human low density lipoprotein receptor promoter: possible regulation sites for sterol-independent transcriptional activation.Biochem. Mol. Biol. Int. 1996; 38: 31-36Google Scholar, 6Lopez J.M. Bennett M.K. Sanchez H.B. Rosenfeld J.M. Osborne T.E. Sterol regulation of acetyl coenzyme A carboxylase: a mechanism for coordinate control of cellular lipid.Proc. Natl. Acad. Sci. USA. 1996; 93: 1049-1053Google Scholar, 7Magana M.M. Osborne T.F. Two tandem binding sites for sterol regulatory element binding proteins are required for sterol regulation of fatty-acid synthase promoter.J. Biol. Chem. 1996; 271: 32689-32694Google Scholar). Although there is overlap in their gene targets, SREBP-2 preferentially enhances genes in the cholesterol synthetic pathway, whereas SREBP-1, particularly 1c, tends to be more active in regulating genes of the fatty acid synthetic pathway (8Shimano H. Horton J.D. Shimomura I. Hammer R.E. Brown M.S. Goldstein J.L. Isoform 1c of sterol regulatory element binding protein is less active than isoform 1a in livers of transgenic mice and in cultured cells.J. Clin. Invest. 1997; 99: 846-854Google Scholar, 9Sheng Z. Otani H. Brown M.S. Goldstein J.L. Independent regulation of sterol regulatory element-binding proteins 1 and 2 in hamster liver.Proc. Natl. Acad. Sci. USA. 1995; 92: 935-938Google Scholar, 10Shimomura I. Bashmakov Y. Shimano H. Horton J.D. Goldstein J.L. Brown M.S. Cholesterol feeding reduces nuclear forms of sterol regulatory element binding proteins in hamster liver.Proc. Natl. Acad. Sci. USA. 1997; 94: 12354-12359Google Scholar, 11Horton J.D. Shimomura I. Brown M.S. Hammer R.E. Goldstein J.L. Shimano H. Activation of cholesterol synthesis in preference to fatty acid synthesis in liver and adipose tissue of transgenic mice overproducing sterol regulatory element-binding protein-2.J. Clin. Invest. 1998; 101: 2331-2339Google Scholar). Characterization and regulation of SREBPs have been extensively studied in several cell culture model systems and, in particular, liver of intact animals [reviewed in ref. (12Horton J.D. Goldstein J.L. Brown M.S. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver.J. Clin. Invest. 2002; 109: 1125-1131Google Scholar)]. Pertinent to the objectives of the present study, previous studies have investigated the effect of dietary fat on the expression of SREBP-1 in liver (13Kim H.J. Takahashi M. Ezaki O. Fish oil feeding decreases mature sterol regulatory element-binding protein 1 (SREBP-1) by down-regulation of SREBP-1c mRNA in mouse liver. A possible mechanism for down-regulation of lipogenic enzyme mRNAs.J. Biol. Chem. 1999; 274: 25892-25898Google Scholar, 14Xu J. Nakamura M.T. Cho H.P. Clarke S.D. Sterol regulatory element binding protein-1 expression is suppressed by dietary polyunsaturated fatty acids. A mechanism for the coordinate suppression of lipogenic genes by polyunsaturated fats.J. Biol. Chem. 1999; 274: 23577-23583Google Scholar). The combined results of these studies demonstrate quite clearly that dietary polyunsaturated fats, either of the n-6 or n-3 class, decrease gene and protein expression of SREBP-1, which in turn are associated with a decrease in fatty acid synthase gene expression. These results have provided a potential mechanism for earlier observations that showed that dietary polyunsaturated fatty acids decrease transcription of genes responsible for controlling hepatic lipogenesis (15Jump D.B. Clarke S.D. Regulation of gene expression by dietary fat.Annu. Rev. Nutr. 1999; 19: 63-90Google Scholar). In addition, from results in SREBP-1c transgenic animals, and in animals in which fasting, refeeding protocols were employed to induce fatty acid biosynthesis, it also seems clear in liver that SREBP-1c regulates fatty acid synthesis (8Shimano H. Horton J.D. Shimomura I. Hammer R.E. Brown M.S. Goldstein J.L. Isoform 1c of sterol regulatory element binding protein is less active than isoform 1a in livers of transgenic mice and in cultured cells.J. Clin. Invest. 1997; 99: 846-854Google Scholar, 16Horton J.D. Bashmakov Y. Shimomura I. Shimano H. Regulation of sterol regulatory element binding proteins in livers of fasted and refed mice.Proc. Natl. Acad. Sci. USA. 1998; 95: 5987-5992Google Scholar). Thus, in liver, SREBP-1c regulates genes of fatty acid biosynthesis and, in turn, SREBP-1 expression is regulated by changes in dietary fat. Although much is known about the regulation of cholesterol and fatty acid synthesis by dietary lipids in liver and how SREBPs might play a role in regulating these pathways, there remains a paucity of information regarding the regulation of these pathways in the intestine. This is unfortunate. The intestine is, after all, the first organ to encounter these dietary lipids (in very substantial amounts) and is responsible for transporting them in a form that can be taken up by peripheral tissues and liver. Our previous efforts have focused on understanding mechanisms for the regulation of intestinal cholesterol metabolism and what roles SREBPs play in this process (17Field F.J. Born E. Murthy S. Mathur S.N. Regulation of sterol regulatory element-binding proteins by cholesterol flux in CaCo-2 cells.J. Lipid Res. 2001; 42: 1687-1698Google Scholar, 18Field F.J. Born E. Murthy S. Mathur S.N. Regulation of sterol regulatory element-binding proteins in hamster intestine by changes in cholesterol flux.J. Biol. Chem. 2001; 276: 17576-17583Google Scholar). There is, however, no information that addresses whether fatty acid synthesis is regulated by changes in fatty acid flux and what role, if any, SREBP-1 or SREBP-2 might have in this process in the gut. The present study was undertaken, therefore, to examine if changes in dietary fatty acid flux regulate intestinal fatty acid biosynthesis and whether SREBPs, particularly SREBP-1c, play a role in fatty acid synthesis in this organ. [3H]water (1 Ci/mmole) was purchased from ICN Biochemicals, Inc., Irvine, CA. Protease inhibitors and Tri Reagent were purchased from Sigma (St. Louis, MO). RNase-free DNase was purchased from Promega Corporation, Madison, WI. Superscript II RNase H-reverse transcriptase was obtained from Invitrogen Life Technologies, Carlsbad, CA. SYBR Green PCR mix was purchased from Applied Biosystems, Foster City, CA. All components for the diets except the oils were purchased from Harlan/Teklad Research Diets, Madison, WI. Corn oil, olive oil, and safflower oil were purchased from a local grocery store. Palm oil was obtained from Craftexpress, Memphis, TN. Fish oil (50:05 TG) was a generous gift from Ocean Nutrition hamsters were purchased from were for a on diet the diets. The animals were fed the diet and the was of the diets is in The start of the dietary was in the hamsters that all animals were fed the diets for of the oil, olive oil, safflower oil, or fish mix in a The lipids from the diet or the cell were with of by of The from the of the diets was and fatty acid were The cellular was on a and with to separate from The from the were by by of and of The was by and were by The was and the was The fatty acids in the were The fatty acid were in and by on a on a a The was to an of for by to it was for The fatty acids were by of with of known fatty acid 2 the of the fatty acids in the acid of the diets of in a The the villus were from duodenum, jejunum, and of the hamster intestine, as by F.J. Born E. Murthy S. Mathur S.N. Regulation of sterol regulatory element-binding proteins in hamster intestine by changes in cholesterol flux.J. Biol. Chem. 2001; 276: 17576-17583Google Scholar). was from the intestinal Tri Two of were with RNase-free DNase to the DNase by of and for 10 the was to by II RNase H-reverse transcriptase for 10 and for the by for of the was with SYBR PCR mix and in a of The were with The were to a single on and by the sequences of the for the PCR was in a model The for 2 and 10 for by of for with for and and for 1 The were as an A of a was on for mRNA and to the levels of the for hamster or acid citrate sterol regulatory element-binding in a sterol regulatory element-binding The for of SREBP in the intestinal by have been F.J. Born E. Murthy S. Mathur S.N. Regulation of sterol regulatory element-binding proteins in hamster intestine by changes in cholesterol flux.J. Biol. Chem. 2001; 276: 17576-17583Google Scholar). Cholesterol and fatty acid synthesis were by of these lipids after of of containing of The in the and fatty acids was as by F.J. Born E. Murthy S. Mathur S.N. Regulation of sterol regulatory element-binding proteins in hamster intestine by changes in cholesterol flux.J. Biol. Chem. 2001; 276: 17576-17583Google Scholar). The of in or fatty protein was as Fatty acid synthase activity in the was as by and S. Fatty acid synthase from Scholar). the intestinal were in and 1 The was for to The or 1 acetyl and The of was in a 1 of the cell or was taken and proteins were by of and of acid to that in protein was the and cholesterol in were the and cholesterol from Cholesterol in the cellular lipids was as earlier F.J. Born E. Murthy S. Mathur S.N. Regulation of sterol regulatory element-binding proteins in hamster intestine by changes in cholesterol flux.J. Biol. Chem. 2001; 276: 17576-17583Google Scholar). whether dietary fatty the were by and by the Inc., Hamsters were fed for 2 diets of and low fat or diets in which the was with the oils palm oil of its fatty acids as olive oil safflower oil or fish oil and the of these animals after the 2 dietary fed palm, olive, and safflower oils of the previous observations (13Kim H.J. Takahashi M. Ezaki O. Fish oil feeding decreases mature sterol regulatory element-binding protein 1 (SREBP-1) by down-regulation of SREBP-1c mRNA in mouse liver. A possible mechanism for down-regulation of lipogenic enzyme mRNAs.J. Biol. Chem. 1999; 274: 25892-25898Google of animals fed the fish oil diet was to animals fed the control of diets on and are from control are from control are from control are from control are from palm oil are from palm oil are from control are from palm oil are from palm oil are from palm oil are from olive oil are from safflower oil are from control are from palm oil are from olive oil are from safflower oil are from control are from palm oil are from safflower oil were the and end of the on the diets. was and cholesterol and as in and The of animals in dietary are from control are from palm oil are from olive oil are from safflower oil in a Hamsters were the and end of the on the diets. was and cholesterol and as in and The of animals in dietary Plasma cholesterol and levels were Plasma cholesterol and were in the palm oil than in and and were in the fish oil than in all examine if the of dietary fat the fatty acid of intestinal the fatty acid of from from duodenum, jejunum, and of animals fed the diets was from the duodenum are as the changes in the proximal intestine were of the changes in and and the the fatty acid in the fat diet is in is clear from these results that intestinal were in the fatty acid that is in the fat cholesterol of from duodenum, jejunum, and were in animals from all dietary of diets on cellular fatty acid acid of cellular was by as in and is the from three animals on the fatty acids are as a of the The in the fatty acid in the oil. in a Fatty acid of cellular was by as in and is the from three animals on the fatty acids are as a of the The in the fatty acid in the oil. the dietary animals were the with the were and three to duodenum, jejunum, and were from the three 1 and and and villus F.J. Born E. Murthy S. Mathur S.N. Regulation of sterol regulatory element-binding proteins in hamster intestine by changes in cholesterol flux.J. Biol. Chem. 2001; 276: 17576-17583Google Scholar). The of fatty acids cholesterol in these cell as an of the rates of synthesis for these The of 1 and 2 the of fatty acids and cholesterol in the cell the villus The the results for the three of the dietary rates of fatty acid synthesis were in of the villus with rates in the rates of fatty acid synthesis were the of the intestine. fatty acid synthesis was by all fat-containing to in fatty acid synthesis a to that in duodenum, except that the fish oil not from fatty acid the palm oil was than There were no in rates of intestinal fatty acid synthesis the animals fed diets in fat. Thus, increased fatty acid flux the proximal intestine decreases the of fatty acid of fatty acid synthesis by fatty acid flux is independent of the of fat of dietary fat on intestinal cholesterol The was the as for except that the of cholesterol was of cholesterol synthesis were also in of the of the diet The of fat not rates of intestinal cholesterol synthesis the villus or the of the the of fat on gene expression of SREBP-1c, and SREBP-2 and their target genes, fatty acid synthase, acetyl-CoA carboxylase, ATP citrate lyase, and HMG-CoA synthase, was from the intestinal cell of duodenum, jejunum, and of animals fed the diets. mRNA levels were by the mRNA levels in the cell populations the villus and combined for the three intestinal In response to the changes were in mRNA levels for SREBP-1a and SREBP-1c, with changes the This is in the combined In the duodenum, mRNA levels of SREBP-1a and were modestly increased in palm or olive oil animals with whereas the of safflower oil no of SREBP-1a and was decreased in fish oil animals with animals ingesting all mRNA levels of SREBP-1c were decreased in duodenum of animals ingesting the polyunsaturated fats, safflower oil, or fish oil with palm or olive oil The changes that were in gene expression of SREBP-1c and in all cell populations the villus with mRNA levels of SREBP-1c in the duodenum of hamsters ingesting palm oil, mRNA levels were decreased in the and villus of hamsters ingesting fish oil. In gene for SREBP-2, HMG-CoA synthase, fatty acid synthase, acetyl-CoA carboxylase, and ATP citrate were not by of the diets whether fatty acid flux SREBP or the of SREBP the dietary were from from the three intestinal and the of SREBP-1 and was these in the duodenum, the of the precursor nor the mature forms of SREBP-1 or SREBP-2 were by of the diets. The results that in the intestine, fatty acid influx fatty acid synthesis without gene expression of three regulatory in the fatty acid synthetic pathway, fatty acid synthase, acetyl-CoA carboxylase, and ATP citrate lyase. be that in animals ingesting fat, fatty acids be decreased to a of for fatty acid synthase and not be to a decrease in fatty acid synthase activity fatty acid synthase activity was in from obtained from duodenum and of animals on the diets these Fatty acid synthase activity was decreased in duodenum of animals ingesting fat with results were in the jejunum, the changes were more than in the the in for fatty acid synthase of the results that in the intact the decrease in intestinal fatty acid synthesis by dietary fatty acids is not to the of for fatty acid synthase is to a effect the The results of the present study clearly demonstrate that the of fat decreases fatty acid synthesis in the proximal intestine. this has not been this In liver, of fatty and acid synthesis has been (15Jump D.B. Clarke S.D. Regulation of gene expression by dietary fat.Annu. Rev. Nutr. 1999; 19: 63-90Google Scholar, J.L. Brown M.S. Regulation of the Scholar, acid Scholar). the intestine, organ that a influx of from intestinal are not in the of lipids for the of an intestinal cell is to lipids and from the to the Thus, it to that lipids might potential regulatory and not an increased influx of cholesterol not of cholesterol synthesis in intestine F.J. Born E. Murthy S. Mathur S.N. Regulation of sterol regulatory element-binding proteins in hamster intestine by changes in cholesterol flux.J. Biol. Chem. 2001; 276: 17576-17583Google Scholar, F.J. Mathur S.N. Regulation of cholesterol metabolism in the 99: Scholar). The that increased fatty acid flux suppressed intestinal fatty acid biosynthesis that there is a mechanism by which fatty acids suppress their synthesis in this organ. in the liver, however, the mechanism is not to an in SREBP or gene expression of in the fatty acid synthetic pathway In the proximal intestine, all diets in fat suppressed fatty acid that of fatty acid synthesis is independent of the of fatty acid in The also that suppression of fatty acid synthesis is to the of fatty acid in the duodenum and jejunum, sites of were rates of fatty acid synthesis the results not a role for intestinal SREBP-1c or the SREBP pathway in regulating fatty acid synthesis fatty acid In the proximal intestine, all dietary suppressed fatty acid biosynthesis, and in animals ingesting fish oil was SREBP-1c gene expression In SREBP-1c gene expression was modestly increased in hamsters fed palm or olive oil. SREBP-1 was not in the of hamsters ingesting fat, fish oil animals in which SREBP-1c gene expression was there was no for regulation of SREBP-1 by the as the of mature to precursor protein was not These with the that the target genes for SREBP-1, fatty acid synthase, acetyl-CoA carboxylase, and ATP citrate were not by fat the that SREBP-1c is not an in regulating fatty acid synthesis fatty acid influx in the intestine. In an earlier study, also a (in intestinal SREBP-1c expression and fatty acid synthesis in hamster intestine changes in intestinal cholesterol flux F.J. Born E. Murthy S. Mathur S.N. Regulation of sterol regulatory element-binding proteins in hamster intestine by changes in cholesterol flux.J. Biol. Chem. 2001; 276: 17576-17583Google Scholar). Thus, in the hamster intestine, of increased fatty acid there is no changes in rates of fatty acid synthesis and SREBP-1c expression. in CaCo-2 with containing fatty acids or rates of fatty acid synthesis were decreased without altering SREBP-1 or mRNA levels of SREBP-1c, fatty acid synthase, or acetyl-CoA carboxylase F.J. Born E. Murthy S. Mathur S.N. fatty acids decrease the expression of sterol regulatory element-binding protein-1 in CaCo-2 effect on fatty acid synthesis and J. 2002; Scholar). in that study, polyunsaturated fatty acids or suppressed fatty acid synthesis and a decrease in expression of In addition, the liver receptor enhanced SREBP-1c gene and protein and in a in fatty acid synthesis F.J. Born E. Murthy S. Mathur S.N. fatty acids decrease the expression of sterol regulatory element-binding protein-1 in CaCo-2 effect on fatty acid synthesis and J. 2002; Scholar). Thus, results obtained in cell culture not what in the intact This seems particularly for the SREBP pathway, as have been in results from cell culture intact animals (1Brown M.S. Goldstein J.L. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor.Cell. 1997; 89: 331-340Google Scholar, 10Shimomura I. Bashmakov Y. Shimano H. Horton J.D. Goldstein J.L. Brown M.S. Cholesterol feeding reduces nuclear forms of sterol regulatory element binding proteins in hamster liver.Proc. Natl. Acad. Sci. USA. 1997; 94: 12354-12359Google Scholar). In the hamster intestine, the results are of changes in cholesterol or fatty acid the SREBP pathway, and in SREBP-1c, has if any, role in regulating fatty acid In the liver, polyunsaturated fatty acids the expression of SREBP-1c with dietary or fatty acids (13Kim H.J. Takahashi M. Ezaki O. Fish oil feeding decreases mature sterol regulatory element-binding protein 1 (SREBP-1) by down-regulation of SREBP-1c mRNA in mouse liver. A possible mechanism for down-regulation of lipogenic enzyme mRNAs.J. Biol. Chem. 1999; 274: 25892-25898Google Scholar, 14Xu J. Nakamura M.T. Cho H.P. Clarke S.D. Sterol regulatory element binding protein-1 expression is suppressed by dietary polyunsaturated fatty acids. A mechanism for the coordinate suppression of lipogenic genes by polyunsaturated fats.J. Biol. Chem. 1999; 274: 23577-23583Google Scholar). n-3 polyunsaturated fatty acids to be more than n-6 polyunsaturated fatty acids in SREBP-1 expression. Our in the intestine the that polyunsaturated fatty particularly n-3 polyunsaturated fatty suppress SREBP-1c mRNA SREBP-1c expression was less in the proximal intestine of safflower oil and fish oil animals with palm oil and olive oil animals, with fish oil more in CaCo-2 containing the polyunsaturated fatty acids or a decrease in and gene expression of SREBP-1 F.J. Born E. Murthy S. Mathur S.N. fatty acids decrease the expression of sterol regulatory element-binding protein-1 in CaCo-2 effect on fatty acid synthesis and J. 2002; Scholar). Thus, not a role of intestinal SREBP-1c in controlling fatty acid synthesis results that polyunsaturated fatty particularly n-3 polyunsaturated fatty suppress mRNA levels of In cell it is that polyunsaturated fatty acids with liver receptor of SREBP-1c J. H. Bashmakov Y. Goldstein J.L. Brown M.S. fatty acids transcription of the sterol regulatory element-binding gene by of the Natl. Acad. Sci. USA. 2001; Scholar). this mechanism for regulating SREBP-1c expression in is The of fat not cholesterol rates of cholesterol or gene expression of SREBP-2 or HMG-CoA might have an increased for cholesterol to and of that the of and dietary cholesterol an possible is synthesized this not it that cholesterol rates of intestinal cholesterol synthesis are to the cholesterol of the intestinal times of enhanced lipoprotein of increased fatty acid flux to intestinal cholesterol synthesis was in earlier also in hamsters J.M. of the fatty acids on hepatic low density lipoprotein receptor activity in the Clin. Invest. 89: Scholar, of dietary fatty acid on cholesterol synthesis and in 25: and in CaCo-2 F.J. Born E. Murthy S. Mathur S.N. fatty acids decrease the expression of sterol regulatory element-binding protein-1 in CaCo-2 effect on fatty acid synthesis and J. 2002; Scholar). fatty acids of and of not SREBP-2 gene or protein that the SREBP-2 pathway was not fatty acid The results are In hamster intestine, increased dietary fatty acid flux not the expression of SREBP-2 nor it cholesterol This was by the The M. S. and J. of of for sterol regulatory element-binding protein

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