SEARCH · PubMed Health

Results for “CHOLESTYRAMINE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,315 records · Page 73Linked to original sources

PubMed1984

Tiflamizole elimination from plasma in rheumatoid arthritis.

Tiflamizole is a fluorinated diarylamidazole sulfone nonsteroidal anti-inflammatory drug not metabolized or excreted in urine. Its mean (+/- SD) elimination t 1/2 from plasma was 21.6 +/- 9 days (range 11.8 to 49.5 days) in 17 subjects with rheumatoid arthritis, and appeared to be first order in most of them. Plasma elimination t 1/2 was loosely related (r = -0.67) to stool frequency in eight subjects for whom stool frequency data were available. In one, cholestyramine decreased t 1/2 to 4.1 days. In two patients, synovial fluid total tiflamizole concentrations were approximately one-third of simultaneous plasma concentrations, but elimination t 1/2s from synovial fluid were of the same order as those from plasma. Even with infrequent dosing, the longer t 1/2 may help sustain the anti-inflammatory effects of this drug.

Adult↗

PubMed1966

Stdies on lipogenesis in vivo. Effects of starvation andre-feeding, and studies on cholesterol synthesis.

1. Studies in vivo have been carried out on hepatic and extrahepatic cholesterol synthesis and also on the effects of starvation and re-feeding on both cholesterol and fatty acid synthesis. 2. In rats and mice fed on a stock diet, extrahepatic tissues accounted for about 4 times as much newly synthesized cholesterol as did the liver. The liver appeared to be somewhat more important in the rat than the mouse. Feeding with cholesterol greatly decreased and cholestyramine greatly increased hepatic cholesterol synthesis without much effect on extrahepatic synthesis. 3. Mice starved for up to 7hr. did not lose any of the ability to convert a [U-(14)C]glucose meal into fat, whereas 18hr. of starvation resulted in an 80% loss of fatty acid synthesis in liver and carcass, an 80% loss in liver cholesterol synthesis and a 65% decrease in carcass cholesterol synthesis; 18hr. of food deprivation also decreased the proportion of counts in epididymal fat pads present as fat and increased the proportion present as glyceride glycerol. 4. Re-feeding for up to 7hr. restored fatty acid synthesis from a [U-(14)C]glucose meal to about 50% of the values for non-starved mice but had no effect on hepatic cholesterol synthesis. The altered distribution of counts in the epididymal fat pads caused by starvation was restored to normal after feeding for 1hr.

Acetates↗

PubMed1972

The role of cytochrome P-450 in cholesterol biogenesis and catabolism.

1. Adjuvant-induced arthritis in rats is accompanied by a loss of activity of the drug-metabolizing enzyme system and a decrease in hepatic cytochrome P-450. 2. Arthritic rats have normal serum and liver cholesterol concentrations. 3. The rate of biogenesis of cholesterol in vivo and in vitro from either [(14)C]acetate or [(14)C]mevalonate in arthritic rats was the same as or greater than that found in control rats. 4. Treatment of rats with carbon disulphide (1ml/kg) resulted in a loss of drug-metabolizing-enzyme activity and increased cholesterol biogenesis. 5. The activity of cholesterol 7alpha-hydroxylase in adjuvant-induced arthritic rats did not differ significantly from that in control rats. 6. Rats fed with cholestyramine had an elevated hepatic cholesterol 7alpha-hydroxylase activity, but neither the concentration of cytochrome P-450 nor the activity of the drug-hydroxylating enzyme, aminopyrine demethylase, was affected. 7. The relationships between drug hydroxylation and cholesterol metabolism are discussed.

Acetates↗

PubMed1976

Equilibrium-dialysis studies of the interaction between cholic acid and 100000g-supernatant preparations from the rat liver.

1. The binding of cholic acid to 100000g supernatants from rat livers was investigated by equilibrium dialysis and gel-exculsion chromatography. 2. Supernatants were found to contain at least two classes of binding site for cholic acid. 3. These recptor molecules are probably proteins since incubation with proteolytic enzymes resulted in complete loss of cholic acid binding. 4. Supernatants were added to columns of Sephadex G-75, and two groups of fractions were shown to bind cholic acid. One of these contained low-affinity binding sites and the other contained both low- and high-affinity binding sites. 5. Feeding cholestyramine had no effect on cholic acid binding. 6. Increased cholic acid binding occurred after injection of phenobarbitone. There was an increase in the amount of the low-affinity component but no change in the high-affinity component. 7. The dissociation constants of the binding of cholic acid suggest that the binding proteins may be involved in bile acid transport.

Animals↗

PubMed1980

3-hydroxy-3-methylglutaryl-coenzyme A reductase A comparison of the modulation in vitro by phosphorylation and dephosphorylation to modulation of enzyme activity by feeding cholesterol- or cholestryamine-supplemented diets.

The activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (hydroxymethylglutaryl-CoA reductase) was considerably inhibited during incubation with ATP+Mg(2+). The inactivated enzyme was reactivated on further incubation with partially purified cytosolic phosphoprotein phosphatase. The inactivation was associated with a decrease in the apparent K(m) of the reductase for hydroxymethylglutaryl-CoA, and this was reversed on reactivation. The slight increase in activity observed during incubation of microsomal fraction without ATP was not associated with a change in apparent K(m) and, unlike the effect of the phosphatase, was not inhibited by NaF. Liver microsomal fraction from rats given cholesterol exhibited a low activity of hydroxymethylglutaryl-CoA reductase with a low apparent K(m) for hydroxymethylglutaryl-CoA. Mícrosomal fraction from rats fed cholestyramine exhibited a high activity with a high K(m). To discover whether these changes had resulted from phosphorylation and dephosphorylation of the reductase, microsomal fraction from rats fed the supplemented diets and the standard diet were inactivated with ATP and reactivated with phosphoprotein phosphatase. Inactivation reduced the maximal activity of the reductase in each microsomal preparation and also reduced the apparent K(m) for hydroxymethylglutaryl-CoA. There was no difference between the preparations in the degree of inactivation produced by ATP. Treatment with phosphatase restored both the maximal activity and the apparent K(m) of each preparation, but never significantly increased the activity above that observed with untreated microsomal fraction. It is concluded that hydroxymethylglutaryl-CoA reductase in microsomal fraction prepared by standard procedures is almost entirely in the dephosphorylated form, and that the difference in kinetic properties in untreated microsomal fraction from rats fed the three diets cannot be explained by differences in the degree of phosphorylation of the enzyme.

Adenosine Triphosphate↗

PubMed1993

Hepatic cholesterol synthesis and the secretion of newly synthesized cholesterol in bile.

To determine the effect of increased hepatic cholesterol synthesis on the secretion of newly synthesized cholesterol in bile, rats were fed with cholestyramine, a bile-acid-binding resin that increases the number of hepatocytes that synthesize cholesterol. Cholesterol synthesis was measured 15 min after [3H]water injection to avoid appreciable exchange between the liver and serum of newly synthesized cholesterol that accumulates in the serum in studies of several hours duration. At 15 min after [3H]water injection, the specific radioactivity of cholesterol in the liver and hepatic microsomes was greatly increased in resin-fed animals compared with controls. However, with resin, the specific radioactivity of newly synthesized cholesterol that was secreted in bile was the same as for controls. At 15 min after [3H]water injection the specific radioactivity of serum cholesterol was minimally increased and not different in resin and control groups. In contrast, in studies that were longer than 60 min, newly synthesized cholesterol in serum was appreciably increased in resin-fed animals, and newly synthesized cholesterol in bile was also greatly increased compared with controls. Thus, when appreciable cholesterol exchange is avoided, an increase in hepatic cholesterol synthesis and the number of hepatocytes that synthesized cholesterol does not result in an increase in newly synthesized cholesterol in bile. Our results suggest that newly synthesized cholesterol is secreted in bile from a fixed subpopulation of hepatocytes. From a comparison of the specific radioactivity of newly synthesized cholesterol in whole liver and bile, it can be estimated that this subpopulation of hepatocytes represents about 20% of the total hepatocyte mass.

Animals↗

PubMed1997

Cholesterol biosynthesis from lanosterol: development of a novel assay method and characterization of rat liver microsomal lanosterol delta 24-reductase.

The membrane-bound sterol delta 24-reductase (24-reductase) catalyses anaerobic reduction of the 24(25)-enes of lanosterol and other obligatory intermediates of cholesterol biosynthesis from lanosterol. A novel assay method and properties of the 24-reductase are described. More than a 120-fold induction of the 24-reductase activity was achieved by feeding rats a diet containing 5% cholestyramine plus 0.1% lovastatin in chow and by modulating diurnal variation. With this enzyme induction condition, lanosterol was converted efficiently into dihydrolanosterol in both intact hepatic microsomes and freshly isolated hepatocytes only when either miconazole or CO was added to inhibit 14 alpha-demethylation of lanosterol. AR45 cells, which are deficient in 14 alpha-methyl demethylase (14 alpha-DM), exhibit lanosterol 24-reductase activity without addition of either CO or miconazole. Conversely, inhibition of the 24-reductase was not required for the expression of 14 alpha-DM activity. Studies on the substrate specificities for the 24-reductase using different 24(25)-enes showed that the most reactive substrate was 5 alpha-cholesta-7,24-dien-3 beta-ol, which exhibited a maximal 18-fold higher kcat than that of lanosterol without the aid of the 14 alpha-DM inhibitor. In addition, both the kinetic behaviour of lanosterol substrate in relation to the 24-reductase and a non-competitive inhibition mode of U18666A (Ki 0. 157 microM) as well as Triparanol (Ki 0.523 microM), two well-known 24-reductase inhibitors, were determined. On the basis of our new findings on the preferred substrate and on the negative effect of 14 alpha-DM on the 24-reductase, we suggest that C-24 reduction of sterols takes place straight after sterol delta 8-->7 isomerization of zymosterol, which occurs several steps after C-32 demethylation of lanosterol in the 19-step pathway of cholesterol biosynthesis from lanosterol.

Animals↗

PubMed1984

The lipid-lowering effects of 3-hydroxy-3-methylglutaric acid and bile acid drainage in WHHL rabbits.

The effect of 3-hydroxy-3-methylglutaric acid (HMG) on serum cholesterol levels was investigated in Watanabe heritable hyperlipidaemic (WHHL) rabbits. Oral administration of HMG resulted in a reduction of serum cholesterol by 39%. Bile acid drainage, by means of either cholestyramine medication or partial ileal bypass (PIB) surgery, also led to significant reductions in circulating cholesterol, by 35 and 59% respectively. Intraperitoneal injection of HMG after PIB surgery further reduced serum cholesterol by 35%. Fibroblasts from the WHHL rabbits did not show high-affinity binding, uptake or degradation of 125I-labelled low density lipoprotein (LDL). The working mechanism of these lipid-lowering lowering therapies in WHHL rabbits is discussed in relation to recent literature. The significant reductions in circulating cholesterol induced by HMG warrant further investigation into the use of this compound in the management of familial hypercholesterolaemia.

Animals↗

PubMed2003

[Pathogenesis and treatment of pruritus in patients with cholestasis].

The pathogenesis of initiating the pruritus in patients with cholestasis is still not completely understood. One hypothesis is, that the cause for initiating the pruritus in patients with cholestasis is the activation of nerves in the skin. The activating substances are unknown, probably they are substances who accumulate in patients with cholestasis. Therefore one of the conventional approaches to treat pruritus is to remove pruritogenic substances from the body. Examples of this approach include the administration of anion exchange resins as cholestyramine or the administration of hepatic enzyme-inducing drugs such as rifampicin or phenobarbital. None of these drugs has been conclusively shown to be efficacious. A new hypothesis is the association of pruritus with altered central neurotransmission. Altered opioid concentrations probably play a central role in the pathogenesis of pruritus. This hypothesis is corroborate by the possibility of treating pruritus in patients with cholestasis with opiate antagonists such as naloxone or nalmefene. The treatment with ondansetron may also have effects on the pruritus of patients with cholestasis. A completely new treatment strategy is the application of dronabinol (r-9-tetrahydrocannabinol).

Brain↗

PubMed1992

[Thrombocytopenia in digitoxin poisoning].

Because she felt unwell, an 80-year-old woman who was receiving treatment with digitoxin (0.07 mg daily) raised the dose on her own initiative to twice or three times the previous level. She then experienced faintness, visual abnormalities and bradyarrhythmia (rate about 40/min). The ECG showed 2 degrees AV block. The digitoxin level was 70.8 ng/ml--far above the upper limit of the therapeutic range (7.5-25 ng/ml). One striking abnormality was thrombocytopenia (33,000/microliters), though the white and red cell counts were normal. Petechiae were not present and there was no evidence of internal bleeding. As the AV block had not produced any critical fall in ventricular rate, there was no need to start treatment with digitalis-binding antibody fragments (Fab fragments). Instead, the patient was given cholestyramine 4 g three times daily with the aim of interrupting the enterohepatic circulation of digitoxin. From then on the rise in platelet count paralleled the fall in digitoxin level. Seven days after discontinuing digitoxin the platelet count reentered the normal range (147,000/microliters). However, the digitoxin level (39.5 mg/ml) was still well above the therapeutic range.

Aged↗

PubMed1991

[Methotrexate in the therapy of primary biliary cirrhosis].

In a pilot study 5 females with primary biliary cirrhosis (PBC), histological stages I-III, were treated with methotrexate (7.5-15.0 mg by mouth weekly) for 15 months. Pruritus and fatigue decreased in 3 patients and cholestyramine could be reduced or discontinued. The concentration of alkaline phosphatase decreased significantly until the 6th month of treatment (P less than 0.002), but only after the methotrexate dosage had been increased to 15 mg weekly. However, the improvement in cholestasis parameters persisted until the end of the period of observation in only 3 patients in stages I and II. In only one case, initially in stage III with increased serum bilirubin concentration of 3.5 mg/dl, was there a change in the histological stage, to stage IV, after treatment. These preliminary results indicate that methotrexate can influence the symptoms and cholestasis enzymes in the early stages of PBC. Controlled studies should therefore only be conducted on anicteric patients in an early stage of the disease.

Adult↗

PubMed1989

[Erythrohepatic protoporphyria with rapidly progressing liver cirrhosis].

A 49-year-old man, known to have had an increased light sensitivity since childhood, was admitted to hospital because of jaundice. Biochemical and morphological examination revealed cirrhosis of the liver with cholestasis. There was a 70-fold increase of protoporphyrin content in the erythrocytes, increased fecal protoporphyrin excretion as well as secondary coproporphyrinuria. Despite symptomatic treatment with ursodeoxycholic acid and cholestyramine hepatic failure ensued for which orthotopic liver transplantation was performed five months after the diagnosis had been made. The patient died two months later of treatment-resistant septicaemia and multiorgan failure. This case demonstrates the need for annual monitoring of liver functions and porphyrin parameters to ensure earliest possible diagnosis of hepatic involvement in erythrohepatic protoporphyria.

Cholestyramine Resin↗

PubMed1995

The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion.

BACKGROUND: Patients with coronary artery disease and abnormalities of serum lipids often have endothelial vasodilator dysfunction, which may contribute to ischemic cardiac events. Whether cholesterol-lowering or antioxidant therapy can restore endothelium-dependent coronary vasodilation is unknown. METHODS: We randomly assigned 49 patients (mean serum cholesterol level, 209 +/- 33 mg per deciliter [5.40 +/- 0.85 mmol per liter]) to receive one of three treatments: an American Heart Association Step 1 diet (the diet group, 11 patients); lovastatin and cholestyramine (the low-density lipoprotein [LDL]-lowering group, 21 patients); or lovastatin and probucol (the LDL-lowering-antioxidant group, 17 patients). Endothelium-dependent coronary-artery vasomotion in response to an intracoronary infusion of acetylcholine (10(-8) to 10(-6) M) was assessed at base line and after one year of therapy. Vasoconstrictor responses to these doses of acetylcholine are considered to be abnormal. RESULTS: Treatment resulted in significant reductions in LDL cholesterol levels of 41 +/- 22 percent in the LDL-lowering-antioxidant group and 38 +/- 20 percent in the LDL-lowering group (P < 0.001 vs. the diet group). The maximal changes in coronary-artery diameter with acetylcholine at base line and at follow-up were -19 and -2 percent, respectively, in the LDL-lowering-antioxidant group, -15 and -6 percent in the LDL-lowering group, and -14 and -19 percent in the diet group (P < 0.01 for the LDL-lowering-antioxidant group vs. the diet group; P = 0.08 for the LDL-lowering group vs. the diet group). (The negative numbers indicate vasoconstriction). Thus, the greatest improvement in the vasoconstrictor response was seen in the LDL-lowering-antioxidant group. CONCLUSIONS: The improvement in endothelium-dependent vasomotion with cholesterol-lowering and antioxidant therapy may have important implications for the activity of myocardial ischemia and may explain in part the reduced incidence of adverse coronary events that is known to result from cholesterol-lowering therapy.

Acetylcholine↗

PubMed1997

The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts.

BACKGROUND: Obstructive changes often occur in aortocoronary saphenous-vein bypass grafts because of atherosclerosis and thrombosis. We studied whether aggressive lowering of low-density lipoprotein (LDL) cholesterol levels or low-dose anticoagulation would delay the progression of atherosclerosis in grafts. METHODS: We studied 1351 patients who had undergone bypass surgery 1 to 11 years before base line and who had an LDL cholesterol level between 130 and 175 mg per deciliter and at least one patent vein graft as seen on angiography. We used a two-by-two factorial design to assign patients to aggressive or moderate treatment to lower LDL cholesterol levels (with lovastatin and, if needed, cholestyramine) and to treatment with warfarin or placebo. Angiography was repeated an average of 4.3 years after base line. The primary angiographic outcome was the mean percentage per patient of grafts with a decrease of 0.6 mm or more in lumen diameter. RESULTS: As measured annually during the study period, the mean LDL cholesterol level of patients aggressive treatment ranged from 93 to 97 mg per deciliter; with moderate treatment, the range was from 132 to 136 mg per deciliter (P<0.001). The mean international normalized ratio was 1.4 in the warfarin group and 1.1 in the placebo group (P<0.001). The mean percentage of grafts with progression of atherosclerosis was 27 percent for patients whose LDL cholesterol level was lowered with aggressive treatment, and 39 percent for those who received moderate treatment (P<0.001). There was no significant difference in angiographic outcome between the warfarin and placebo groups. The rate of revascularization over four years was 29 percent lower in the group whose LDL cholesterol level was lowered aggressively than in the group receiving moderate treatment (6.5 percent vs. 9.2 percent, P= 0.03). CONCLUSIONS: Aggressive lowering of LDL cholesterol levels to below 100 mg per deciliter reduced the progression of atherosclerosis in grafts. Low-dose warfarin did not reduce the progression of atherosclerosis.

Adult↗

PubMed1979

Immunotitration of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in various physiological states.

The immunotitration of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase [mevalonate:NADP+ oxidoreductase [CoA-acylating), EC 1.1.1.34], the major regulatory enzyme in cholesterol biosynthesis, by HMG-CoA reductase antiserum is described. This technique provides the advantage that one can rapidly measure relative changes in both enzyme concentration and enzyme activity in different physiological states by using enzyme samples all the way from crude liver microsomes to purified enzyme. Regarding the diurnal rhythm of HMG-CoA reductase, the major difference noted between animals killed near the middle of the dark period (D 4.5) compared to animals killed near the middle of the light period (L 4.5) was in the concentrations of HMG-CoA reductase present, rather than in the activity of the enzyme, with substantially more enzyme found near mid-dark. Cholestyramine treatment resulted in both an increased concentration of HMG-CoA reductase and a catalytically more active enzyme. On the other hand, cholesterol feeding resulted in both a decreased concentration of HMG-CoA reductase and a catalytically less active enzyme.

Animals↗

PubMed1983

Cholesterol synthesis and low density lipoprotein uptake are regulated independently in rat small intestinal epithelium.

We have compared the rates of low density lipoprotein (LDL) uptake and cholesterol synthesis in the rat intestine. By using a constant infusion technique, total and receptor-independent uptake was determined with homologous rat LDL (rLDL) and methylated human LDL (Me-hLDL), respectively. The absolute rates of sterol synthesis were measured with [1-(14) C]-octanoate and [3H]water. The rates of rLDL uptake in whole gut segments were similar along the length of the small intestine, whereas the rates of sterol synthesis varied over a 5-fold range and were highest in the duodenum and distal ileum. When the mucosal epithelium was fractionated along the villus/crypt axis, both rLDL and Me-hLDL clearance by the enterocytes increased approximately 3-fold in going from the upper villus to the crypt cell fractions, in both jejunum and ileum. In both the whole gut segments and isolated cells, approximately 60% of LDL uptake was receptor dependent. When the rates of rLDL cholesterol uptake were calculated and related to the absolute rates of sterol synthesis in the same cell fractions in vivo, both processes were found to be distributed similarly along the villus/crypt axis. Furthermore, the majority of mucosal cholesterol (64-86%) was derived from local synthesis rather than from rLDL uptake at all locations along the intestinal villus. Finally, when sterol synthesis in the epithelial cells was varied up to 7-fold by feeding cholesterol, triglyceride, cholestyramine, or surfomer, rLDL uptake was essentially unchanged. Thus, in intestinal epithelial cells in vivo, the rate of LDL uptake was constant under circumstances in which changing needs for cellular cholesterol were met by changes in the rates of sterol synthesis.

Animals↗

PubMed1988

Lovastatin, an inhibitor of cholesterol synthesis, induces hydroxymethylglutaryl-coenzyme A reductase directly on membranes of expanded smooth endoplasmic reticulum in rat hepatocytes.

Lovastatin is a potent competitive inhibitor of the rate-limiting enzyme of cholesterol synthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (NADPH) [HMG-CoA reductase; (S)-mevalonate:NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34]. We determined the subcellular distribution of HMG-CoA reductase at high resolution by means of immunoelectron microscopy on ultrathin frozen liver sections of rats treated with lovastatin and cholestyramine. High concentrations of reductase were located on the outer (cytoplasmic) surfaces of smooth endoplasmic reticulum (SER) membranes induced in hepatocytes by acute drug administration. The enzyme was specifically localized over the whorled SER membranes and was absent from nonwhorled SER, rough endoplasmic reticulum, and peroxisomes. Intense HMG-CoA reductase labeling was only observed in hepatocytes containing high levels of HMG-CoA reductase activity; no staining was detected in untreated livers. These observations show that HMG-CoA reductase is induced as an integral component of the SER membranes that form in rat hepatocytes subsequent to lovastatin treatment and suggest that the formation of SER whorls in rat hepatocytes is due to mechanism-based effects of lovastatin.

Animals↗

PubMed2001

Regulation of sterol regulatory element-binding proteins in hamster intestine by changes in cholesterol flux.

A control chow diet or diets containing 1% cholesterol (cholesterol-enriched) or 4% cholestyramine and 0.15% lovastatin (cholesterol-depletion) were fed to hamsters for 2 weeks. Sterol regulatory element-binding protein (SREBP)-1a, SREBP-1c, SREBP-2, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, 3-hydroxy-3-methylglutaryl-coenzyme A synthase, and LDL receptor mRNA levels and SREBP-1 and -2 protein expression were estimated in villus cell populations from duodenum, jejunum, and ileum. SREBP-1a was a minor transcript in hamster intestine, and its gene expression was not altered by changes in dietary cholesterol flux. In contrast, SREBP-1c gene expression was increased by dietary cholesterol and decreased by cholesterol depletion. mRNA levels for SREBP-2 and the other sterol-responsive genes were increased in intestines of animals on the cholesterol depletion diet but minimally suppressed if at all, by the diet enriched in cholesterol. In general, the amount of the precursor form of SREBP-1 was higher in cells of the upper villus and lower in cells of the lower villus. SREBP-2 precursor was higher in cells of the lower villus and lower in cells of the upper villus. Protein expression of precursor correlated with the location of gene expression for SREBPs. The amount of precursor mass of SREBP-2 was not altered by cholesterol feeding but was increased by cholesterol depletion. The mature form of SREBP-2 was in very low abundance and difficult to detect in intestines of animals fed control chow or cholesterol. It was readily detectable and increased in intestines of animals on the cholesterol-depletion diet. The diets did not significantly alter the amount of precursor or mature forms of SREBP-1. Cholesterol feeding had no effect on cholesterol or fatty acid synthesis, whereas synthesis of these lipids was increased in intestines of hamsters on the cholesterol-depleted diet. These results suggest that SREBP-1a has little or no role in regulating intestinal cholesterol synthesis. It is postulated that under basal conditions, SREBP-1c regulates intestinal fatty acid synthesis and SREBP-2 regulates cholesterol synthesis. Following marked changes in cholesterol flux across the intestine, SREBP-2 assumes the role of SREBP-1 and regulates both cholesterol and fatty acid synthesis in intestine.

Animals↗