The effects of dietary linoleic acid on reducing serum cholesterol and atherosclerosis development are nullified by a high-cholesterol diet in male and female apoE-deficient mice.

Linoleic acid (LA) has a two-sided effect with regard to serum cholesterol-lowering and pro-inflammation, although whether this fatty acid reduces serum cholesterol and the development of atherosclerosis under high-cholesterol conditions has yet to be ascertained. In this study, we examine the effects of dietary LA on reducing serum cholesterol and atherosclerosis development under high-cholesterol conditions. Male and female apoE-deficient (ApoE-/-) mice were fed AIN-76-based diets containing 10% SFA and 0·04 % cholesterol, 10% LA and 0·04% low cholesterol (LALC), or 10% LA and 0·1% high cholesterol (LAHC) for 9 weeks. The results revealed significant reduction in serum cholesterol levels and aortic lesions with increasing levels of pro-inflammatory biomarkers (urinary isoprostane and aortic MCP-1 mRNA) in male and female LALC groups compared with those in the SFA groups (P < 0·05). Furthermore, whereas there were significant increases in the serum cholesterol levels and aortic lesions (P < 0·05), there was no difference in aortic MCP-1 mRNA levels in male and female LAHC groups compared with those in the LALC groups. A high-dietary intake of cholesterol eliminated the serum cholesterol-lowering activity of LA but had no significant effect on aortic inflammation in either male or female ApoE-/- mice. The inhibitory effect of LA on arteriosclerosis is cancelled by a high-cholesterol diet due to a direct increase in serum cholesterol levels. Accordingly, serum cholesterol levels might represent a more prominent pathogenic factor than aortic inflammation in promoting the development of atherosclerosis.

Inhibition of Niemann-Pick C1-Like 1 by Ezetimibe Reduces Dietary 5ß,6ß-Epoxycholesterol Absorption in Rats.

PURPOSE: Oxycholesterols (OCs) are produced from cholesterol by oxidation of the steroidal backbone and side-chain. OCs are present in blood and evidence suggests their involvement in disease development and progression. However, limited information is available regarding the absorption mechanisms and relative absorption rates of dietary OCs. Although ezetimibe is known to inhibit intestinal cholesterol absorption via Niemann-Pick C1-Like 1 (NPC1L1), whether it also inhibits dietary OC absorption is unclear. METHODS: We investigated the effects of ezetimibe on OC absorption in rats fed an OC-rich diet containing 10 different OCs. We collected lymphatic fluid using permanent cannulation of the thoracic duct and quantified OC levels. RESULTS: Ezetimibe treatment significantly reduced the apparent absorption of 5ß,6ß-epoxycholesterol (5,6ß-epoxy) and its levels in the proximal intestinal mucosa in OC-fed rats. Using in silico analyses, the binding energy of NPC1L1 N-terminal domain (NPC1L1-NTD) and 5,6ß-epoxy was found to be similar to that of NPC1L1-NTD and cholesterol, suggesting that polar uncharged amino acids located in the steroidal part of 5,6ß-epoxy were involved. CONCLUSION: Our results indicate that ezetimibe-mediated inhibition of dietary OC absorption varies depending on the specific OC, and only the absorption of 5,6ß-epoxy is significantly reduced.

Taurine ameliorates cholesterol metabolism by stimulating bile acid production in high-cholesterol-fed rats.

This study was designed to investigate the effects of dietary taurine on cholesterol metabolism in high-cholesterol-fed rats. Male Sprague-Dawley rats were randomly divided into two dietary groups (n = 6 in each group): a high-cholesterol diet containing 0.5% cholesterol and 0.15% sodium cholate, and a high-cholesterol diet with 5% (w/w) taurine. The experimental diets were given for 2 weeks. Taurine supplementation reduced the serum and hepatic cholesterol levels by 37% and 32%, respectively. Faecal excretion of bile acids was significantly increased in taurine-treated rats, compared with untreated rats. Biliary bile acid concentrations were also increased by taurine. Taurine supplementation increased taurine-conjugated bile acids by 61% and decreased glycine-conjugated bile acids by 53%, resulting in a significant decrease in the glycine/taurine (G/T) ratio. Among the taurine-conjugated bile acids, cholic acid and deoxycholic acid were significantly increased. In the liver, taurine supplementation increased the mRNA expression and enzymatic activity of hepatic cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme for bile acid synthesis, by three- and two-fold, respectively. Taurine also decreased the enzymatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP). These observations suggest that taurine supplementation increases the synthesis and excretion of taurine-conjugated bile acids and stimulates the catabolism of cholesterol to bile acid by elevating the expression and activity of CYP7A1. This may reduce cholesterol esterification and lipoprotein assembly for very low density lipoprotein (VLDL) secretion, leading to reductions in the serum and hepatic cholesterol levels.

Unavailability of liver triacylglycerol increases serum cholesterol concentration induced by dietary cholesterol in exogenously hypercholesterolemic (ExHC) rats.

BACKGROUND: Exogenously hypercholesterolemic (ExHC) rats develop hypercholesterolemia and low hepatic triacylglycerol (TAG) levels when dietary cholesterol is loaded. The responsible gene Smek2 was identified via linkage analysis using the original strain Sprague-Dawley (SD) rats. In this study, we compared SD and ExHC rats to investigate a relationship between hypercholesterolemia and the low hepatic TAG levels observed in ExHC rats. METHODS: Male 4-weeks-old ExHC and SD rats were fed a 1% cholesterol diet for 1 week. Serum and liver parameters were analyzed. Gene expression and enzyme activities related to TAG metabolism were also assessed. RESULTS: We reproducibly observed higher serum cholesterol and lower hepatic TAG levels in ExHC rats than in SD rats. Golgi apparatus in the livers of ExHC rats secreted ß-very-low-density lipoprotein (ß-VLDL) that had higher cholesterol ester (CE) and lower TAG content than those in the ß-VLDL secreted by SD rats. Gene expression related to fatty acid and TAG synthesis in ExHC rats was lower than that in SD rats. Enzymatic activities for fatty acid synthesis were also relatively lower in ExHC rats. Moreover, the fatty acid composition of hepatic and serum CE in ExHC rats showed that these CEs were not modified after secretion from the liver despite the similar activities of serum lecithin-cholesterol acyltransferase (LCAT) in ExHC rats to those in SD rats. CONCLUSIONS: Low production of liver TAG and secretion of CE-rich, TAG-poor ß-VLDL without modification by LCAT in the circulation contributed to hypercholesterolemia induced by dietary cholesterol in ExHC rats.

Mutation in Smek2 regulating hepatic glucose metabolism causes hypersarcosinemia and hyperhomocysteinemia in rats.

Suppressor of mek1 (Dictyostelium) homolog 2 (Smek2), was identified as one of the responsible genes for diet-induced hypercholesterolemia (DIHC) of exogenously hypercholesterolemic (ExHC) rats. A deletion mutation in Smek2 leads to DIHC via impaired glycolysis in the livers of ExHC rats. The intracellular role of Smek2 remains obscure. We used microarrays to investigate Smek2 functions with ExHC and ExHC.BN-Dihc2BN congenic rats that harbor a non-pathological Smek2 allele from Brown-Norway rats on an ExHC background. Microarray analysis revealed that Smek2 dysfunction leads to extremely low sarcosine dehydrogenase (Sardh) expression in the liver of ExHC rats. Sarcosine dehydrogenase demethylates sarcosine, a byproduct of homocysteine metabolism. The ExHC rats with dysfunctional Sardh developed hypersarcosinemia and homocysteinemia, a risk factor for atherosclerosis, with or without dietary cholesterol. The mRNA expression of Bhmt, a homocysteine metabolic enzyme and the hepatic content of betaine (trimethylglycine), a methyl donor for homocysteine methylation were low in ExHC rats. Results suggest that homocysteine metabolism rendered fragile by a shortage of betaine results in homocysteinemia, and that Smek2 dysfunction causes abnormalities in sarcosine and homocysteine metabolism.

Ezetimibe inhibits lymphatic transport of esterified cholesterol but not free cholesterol in thoracic lymph duct-cannulated rats.

PURPOSE: Ezetimibe has been shown to inhibit dietary cholesterol absorption in animal models and humans, but studies on lymphatic lipid transport have not yet been performed. Rats subjected to permanent lymph duct cannulation were used to investigate the effects of ezetimibe on lipid transport. METHODS: Rats were fed diets with and without ezetimibe (5.0 mg/kg), and their lymph was collected after feeding to quantify lymphatic lipid levels. Total cholesterol content in the intestinal mucosa was also measured. RESULTS: Rats that consumed ezetimibe had significantly lower lymphatic total cholesterol transport with the reduction of esterified cholesterol transport. According to the calculation based on cholesterol consumption, ezetimibe reduced the total cholesterol lymphatic recovery rate by 54 %. We also determined that ezetimibe significantly reduced the total cholesterol content in the intestinal mucosa. CONCLUSION: This is the first direct evidence that ezetimibe inhibits esterified but not free cholesterol lymphatic transport in thoracic duct-cannulated rats. The results also indicate that ezetimibe is not involved in the lymphatic transport of triacylglycerols, phospholipids, or α-tocopherol.

SHRSP/Izm and WKY/NCrlCrlj rats having a missense mutation in Abcg5 deposited plant sterols in the body, but did not change their biliary secretion and lymphatic absorption-comparison with Jcl:Wistar and WKY/Izm rats.

We had previously found plant sterols deposited in the bodies of stroke-prone spontaneously hypertensive rats (SHRSP)/Sea and Wistar Kyoto (WKY)/NCrlCrlj rats that had a missense mutation in the Abcg5 cDNA sequence that coded for ATP-binding cassette transporter (ABC) G5. We used SHRSP/Izm, WKY/NCrlCrlj, and WKY/Izm rats in the present study to determine the mechanisms for plant sterol deposition in the body. Jcl:Wistar rats were used as a control strain. A diet containing 0.5% plant sterols fed to the rats resulted in plant sterol deposition in the body of SHRSP/Izm, but not in WKY/Izm or Jcl:Wistar rats. Only a single non-synonymous nucleotide change, G1747T, resulting in a conservative cysteine substitution for glycine at amino acid 583 (Gly583Cys) in Abcg5 cDNA was identified in the SHRSP/Izm and WKY/NCrlCrlj rats. However, this mutation was not found in the WKY/Izm or Jcl:Wistar rats. No significant difference in the biliary secretion or lymphatic absorption of plant sterols was apparent between the rat strains with or without the missense mutation in Abcg5 cDNA. Our observations suggest that plant sterol deposition in rat strains with the missense mutation in Abcg5 cDNA can occur, despite there being no significant change in the biliary secretion or lymphatic absorption of plant sterols.

Diet and atherosclerosis in apolipoprotein E-deficient mice.

Atherosclerosis is a multifactorial, long-lasting process in humans. Accordingly, animal models in which more rapid changes occur can be useful for the study of this process. Among such models are apolipoprotein E-deficient (apoE-/-) mice, which give insight into the human process. ApoE-/- mice show impaired clearing of plasma lipoproteins and develop atherosclerosis in a short time, and hence they are an excellent model in which to assess the impact of dietary factors. This review considers lipid metabolism and inflammation as well as nutritional constituents affecting atherosclerosis, with reference to apoE-/- mice, and discusses the mechanisms through which they act.

Effect of a liver X receptor agonist on deposition and lymphatic absorption of plant sterols in stroke-prone spontaneously hypertensive rats having a mutation in ATP-binding cassette transporter G5.

The effects were compared of T0901317, a liver X receptor agonist, on deposition in the liver and serum and lymphatic absorption of plant sterols in stroke-prone spontaneously hypertensive rats (SHRSPs) having a missense mutation in Abcg5, which codes for ATP-binding cassette transporter (ABC) G5, with those in Wistar rats. Both strains were pair-fed for 7 d with a 0.5% plant sterol diet with or without 5 mg/kg of body weight of T0901317. The deposition of plant sterols in the liver and serum was higher in SHRSPs than in Wistar rats. A significant reduction of plant sterol deposition was observed in Wistar rats, but not in SHRSPs when T0901317 was given. Both strains were then fed for 7 d with a control diet with or without T0901317. The lymphatic absorption of plant sterols was reduced to almost half the normal level by the T0901317 treatment. However, no difference in absorption was apparent between SHRSPs and Wistar rats regardless of the T0901317 treatment. These results suggest that the plant sterol deposition in SHRSPs was not necessarily caused by the increased absorption of plant sterols.

Vasodilating dipeptide Trp-His can prevent atherosclerosis in apo E-deficient mice.

Most of the investigations for an alternative medicinal treatment on atherosclerosis have been focused on natural or dietary compounds including phytochemicals. So far, few studies regarding anti-atherosclerotic small peptides except for tetrapeptide of Lys-Arg-Glu-Ser have been reported. The present study was, thus, to investigate whether dipeptide Trp-His, which is one of vasodilating small peptides, could reduce atherosclerotic lesions in apo E-deficient mice fed a high-fat diet. The animal study involved a 9-week-successive administration of Trp-His at a dose of 0, 10 or 100 mg/kg per d. After 9-week administration, en face analyses provided the first direct evidence that the atherosclerotic lesion area was significantly reduced by 27 and 38 % for Trp-His dosed at 10 and 100 mg/kg per d, respectively, compared with the control group. Administration of Trp-His did not affect growth parameters such as body weight and feeding efficiency (P>0.1). Total serum cholesterol and HDL-cholesterol as well as lipid profiles in the liver did not differ between the tested groups. Taken together, the anti-atherosclerotic effect of dipeptide Trp-His should be addressed into physiological functions of bioactive peptides, in which the dipeptide may elicit the power by alternative mechanism(s), not by the regulation of lipid metabolism.

Effects of Kurozu concentrated liquid on adipocyte size in rats.

BACKGROUND: Kurozu concentrated liquid (KCL) is used as a health-promoting supplement for the treatment of disorders such as cancer, hyperlipidemia, and hypertension in Japan. We investigated the possible anti-obesity effects of KCL in rats. METHODS: Male Sprague Dawley rats were fed American Institute of Nutrition 76 formula diet and were orally administrated KCL or acetic acid at a dose of 100 mg/kg body weight or deionized water for 4 weeks. Adipocyte size, DNA content in subcutaneous adipose tissue, lipid levels in the serum and liver, and the rate of fatty acid excretion were determined. Effects of KCL on pancreatic lipase activity and 3T3-L1 preadipocyte differentiation were investigated in vitro. RESULTS: In the KCL group, the average adipocyte size in subcutaneous and perirenal adipose tissues was significantly reduced. The KCL-administered rats displayed greater numbers of small adipocytes in the subcutaneous, perirenal and mesenteric adipose tissues than did rats from the other groups. In the KCL group, the DNA content in subcutaneous adipose tissue was significantly increased. The rate of fatty acid excretion was significantly increased in the KCL group. Furthermore, KCL significantly inhibited pancreatic lipase activity in vitro, and also significantly inhibited fat accumulation and mRNA expression of fatty acid binding protein 2 (aP2) and peroxisome proliferator-activated γ (PPARγ) in 3T3-L1 preadipocyte. The levels of serum and liver lipids, the concentration of serum glucose, and the levels of adiponectin were similar among the 3 groups. CONCLUSION: Oral administration of KCL decreases the adipocyte size via inhibition of dietary fat absorption and reductions of PPARγ and aP2 mRNA expression levels in adipocytes.

Low utilization of glucose in the liver causes diet-induced hypercholesterolemia in exogenously hypercholesterolemic rats.

Exogenously hypercholesterolemic (ExHC) rats develop diet-induced hypercholesterolemia (DIHC) when fed with dietary cholesterol. Previously, we reported that, under the high-sucrose-diet-feeding condition, a loss-of-function mutation in Smek2 results in low activity of fatty acid synthase (FAS) followed by the shortage of hepatic triacylglycerol content in ExHC rats and the onset of DIHC. However, the relationship between the Smek2 mutation and FAS dysfunction is still unclear. Here, we focused on carbohydrate metabolism, which provides substrates for FAS, and analyzed carbohydrate and lipid metabolisms in ExHC rats to clarify how the deficit of Smek2 causes DIHC. Male ExHC and SD rats were fed high-sucrose or high-starch diets containing 1% cholesterol for 2 weeks. Serum cholesterol levels of the ExHC rats were higher, regardless of the dietary carbohydrate. Hepatic triacylglycerol levels were higher in only the SD rats fed the high-sucrose diet. Moreover, the ExHC rats exhibited a diabetes-like status and accumulation of hepatic glycogen and low hepatic mRNA levels of liver-type phosphofructokinase (Pfkl), which encodes a rate-limiting enzyme for glycolysis. These results suggest that the glucose utilization, particularly glycolysis, is impaired in the liver of ExHC rats. To evaluate how the diet with extremely low glucose affect to DIHC, ExHC.BN-Dihc2BN, a congenic strain that does not develop DIHC, and ExHC rats were fed a high-fructose diet containing 1% cholesterol for 2 weeks. The serum cholesterol and hepatic triacylglycerol levels were similar in the strains. Results of water-soluble metabolite analysis with primary hepatocytes, an increase in fructose-6-phosphate and decreases in succinate, malate and aspartate in ExHC rats, support impaired glycolysis in the ExHC rats. Thus, the Smek2 mutation causes abnormal hepatic glucose utilization via downregulation of Pfkl expression. This abnormal glucose metabolism disrupts hepatic fatty acid synthesis and causes DIHC in the ExHC rats.

Milk fermented by Lactobacillus gasseri SBT2055 influences adipocyte size via inhibition of dietary fat absorption in Zucker rats.

We have demonstrated previously that a diet containing skimmed milk (SM) fermented by Lactobacillus gasseri SBT2055 (LGSP) reduces adipocyte size in Sprague-Dawley rats. Two experiments were conducted to extend these observations in order to elucidate the mechanism involved. In experiment 1, lean and obese Zucker rats were fed a diet containing SM or LGSP for 4 weeks. The LGSP diet, compared with the SM diet, resulted in lowering of the mesenteric adipose tissue weight (23 %; P < 0.05), adipocyte sizes (28 %; P < 0.001) and serum leptin concentration (36 %; P < 0.05) in lean rats. Obese Zucker rats did not display such dietary effects. Only the number of smaller adipocytes was increased (P < 0.05) by the LGSP diet in the subcutaneous adipose tissue of obese rats. The LGSP diet significantly reduced the serum and hepatic cholesterol in rats. In addition, the LGSP diet led to an increased excretion of faecal fatty acids and total neutral faecal sterols in both rat strains. In experiment 2, Sprague-Dawley rats with permanent cannulation of the thoracic duct were fed either the SM or LGSP diets and their lymph was collected. The LGSP diet lowered the maximum transport rate of TAG and phospholipids. These results indicate that fermented milk regulates adipose tissue growth through inhibition at the stage of dietary fat absorption in lean Zucker rats.

Missense mutation of Abcg5 in stroke-prone spontaneously hypertensive rats does not influence lymphatic sitosterol absorption regardless of the dose: comparison with Wistar rats.

The lymphatic recovery of radiolabeled sitosterol administered in various amounts to the stomach was almost the same between stroke-prone spontaneously hypertensive rats (SHRSPs), a strain having a missense mutation in ATP binding cassette transporter g5 (Abcg5), and Wistar rats, a normal strain. The results suggest that the mutation of Abcg5 in SHRSPs, compared with Wistar rats, did not influence the ability for intestinal sitosterol absorption regardless of the dose.

Missense mutation in Abcg5 in SHRSP rats does not accelerate intestinal absorption of plant sterols: comparison with Wistar rats.

Stroke-prone spontaneously hypertensive rats (SHRSP) deposit plant sterols in their bodies and have a mutation in ATP binding cassette transporter G5 (Abcg5). Lymphatic recovery rates of campesterol and sitosterol in SHRSP rats were comparable to those in Wistar rats, a strain that does not deposit plant sterols in the body and has no mutation in Abcg5. Higher absorption of stigmasterol and sitostanol was observed in SHRSP rats than in Wistar rats, but the differences between SHRSP and Wistar rats were quite small, because the absorbed amounts of these two sterols were much lower than those of campesterol and sitosterol. The in situ uptake of (3)H-sitosterol and (14)C-cholesterol solubilized in the bile salt micelle into intestinal mucosa was comparable between SHRSP and Wistar rats. These observations suggest that a mutation in Abcg5 does not greatly influence intestinal absorption of plant sterols in SHRSP rats, at least in comparison with Wistar rats.

Dietary pine bark extract reduces atherosclerotic lesion development in male ApoE-deficient mice by lowering the serum cholesterol level.

Pine bark extract (PBE) mainly contains proanthocyanidin in oligomers. It has many physiological effects, including antioxidant, anti-inflammatory, and so on. In this study, we investigated whether PBE has an anti-atherogenic effect on apoE-deficient mice. Male and female mice were fed a diet based on an AIN-76 formula (control diet), and that diet supplemented with 2% PBE (the PBF diet). The PBE diet, compared with the control diet, resulted in lowering the body weight gain and the adipose tissue weight in both male and female mice. The lesion area of the valve and the levels of serum and liver cholesterol in the male mice decreased on the PBE diet. The PBE diet had no significant effect on the levels of urinary isoprostanes or serum thiobarbituric acid reactive substances. These results indicate that dietary PBE can have beneficial effects on atherosclerosis development in male apoE-deficient mice by lowering the serum cholesterol level.

The inhibitory effect on aldose reductase by an extract of Ganoderma lucidum.

The human aldose reductase inhibitory effects of the methanol extracts of 17 medicinal and edible mushrooms were examined. Ganoderma lucidum showed the highest aldose reductase inhibitory activity compared with the other mushrooms. The effect of an ethanol extract of G. lucidum on the galactitol level in the eye lens was studied in a galactosemic rat model in vivo. This mushroom significantly decreased the galactitol accumulation.

A comparison of the potential unfavorable effects of oxycholesterol and oxyphytosterol in mice: different effects, on cerebral 24S-hydroxychoelsterol and serum triacylglycerols levels.

Sterol oxidation products derived from cholesterol and phytosterol are formed during the processing and storage of foods. The objective of the present study was to assess the potential unfavorable effects of oxysterols in mice. C57BL/6J mice were fed an AIN-93G-based diet containing 0.2 g/kg of oxycholesterol or oxyphytosterol for 4 weeks. The most abundant oxysterol in the diet was 7-ketosterol, but alpha-epoxycholesterol, beta-epoxycholesterol, or 7alpha-hydroxyphytosterol, and 7beta-hydroxyphytosterol were more prominent than 7-ketosterol in the serum and liver respectively. Consumption of both oxysterols resulted in an increased in 4beta-hydroxycholesterol and total oxycholesterol in the liver, but the oxycholesterol-fed mice had a lower level of cerebral 24S-hydroxycholesterol and a higher level of the serum triacylglycerols than the control and oxyphytosterol groups. These results indicate that both oxysterols in the diet are accumulated in the body, but that the biological effect of oxycholesterol is different from that of oxyphytosterol.

Mechanism for the cholesterol-lowering action of egg white protein in rats.

Eggs are a popular source of dietary cholesterol, but their consumption does not necessarily result in an increased serum cholesterol concentration. We investigated the cholesterol-lowering activity of egg white protein (EWP) and its potential mechanism in rats. The consumption of EWP resulted in a decreased concentration of cholesterol in the serum, liver and intestinal mucosa. The excretion of fecal neutral sterols and bile acids was greater by rats fed with EWP than by those fed with casein. The ratio of cholesterol and bile acids in the micellar phase to those in the solid phase was lower in the intestinal contents from rats fed with EWP than from those fed with casein. These results suggest that the cholesterol-lowering activity of EWP can be attributed to lowering the cholesterol absorption by intervening in the micellar formation in the intestines.

LXR agonist increases the lymph HDL transport in rats by promoting reciprocally intestinal ABCA1 and apo A-I mRNA levels.

Liver and intestine are major sites of apo A-I synthesis in mammals. ABCAI is reported to be involved in the secretion of nascent HDL from cultured intestinal cells. However, whether ABCA1 participates in the secretion of nascent HDL from the intestine has not been assessed directly in vivo. This study examined the effect of a synthetic LXR-agonist "TO" on the lymphatic transport of HDL in thoracic duct-cannulated rats. The feeding of a TO-containing diet resulted in an increased transport of cholesterol and apo A-I in the lymph d > 1.063 g/ml lipoprotein fraction than did the feeding of a control diet without TO. The transport of cholesterol in whole lymph was lower, whereas the transport of apo A-I was higher, in the TO group. The abundance of mRNAs for ABCAI and apo A-I in the intestine was increased in the TO group. Furthermore, although the TO-containing diet reportedly increased the serum HDL concentration in intact mice and rats, no such effect was observed in the cannulated rats. The LXR agonist stimulated in vivo the synthesis of nascent HDL by increasing reciprocally the mRNA for ABCAI and apo A-I in the intestine, thereby contributing to an increase in the circulating HDL.