Influence of partial replacement of starch by sucrose in high fat-cholesterol diet on serum lipoprotein responses of cynomolgus monkeys

The influence of partial replacement of starch by sucrose on dietary cholesterol-induced serum lipoprotein responses was examined in 10 male cynomolgus monkeys (Macaca fascicularis). In a crossover design two semipurified diets provided either starch or starch and sucrose (1:1) as carbohydrate (49% by calories) with 0.4 mg cholesterol/kcal. Six weeks of starch + sucrose diet resulted in significantly reduced levels (mean +/- SE, mg/dl) of serum total cholesterol (264 +/- 9 vs 244 +/- 8) and apo B (110 +/- 6 vs 96 +/- 6) when compared with starch diet, whereas serum triglyceride levels remained similar between diets. With respect to changes in lipids and apolipoproteins (A-I or B) of very low (VLDL), low (LDL), intermediate (IDL), and high (HDL) density lipoproteins, starch + sucrose diet significantly increased VLDL-apo B (+34%), and decreased LDL-cholesterol (-18%) and LDL-apo B (-15%) as compared with starch alone; no differences were found in IDL and HDL between diets. The relative proportion of starch to sucrose in a diet appears to influence the magnitude of response of lipoproteins to dietary cholesterol.     

Effect of qualitatively different carbohydrates on the lipoprotein spectrum and lipid composition of the blood in experimental animals]

Experiments on rats demonstrated that a high-carbohydrate diet with starch produced no changes in the lipoprotein composition and lipid concentration in the blood. Diets containing sucrose promoted an increase in triglycerides and of the pre-beta-lipoproteins. However, the effect of sucrose depended on the qualitative correlation of the carbohydrate and lipid components of the diet. A reduction of lipoproteins of low density and of the total cholesterol/phospholipid ratio on account of an increase of the latter in the blood was seen in rats given sucrose in the composition of the high-carbohydrate diet with a decreased amount of the saturated fat. Inclusion of sucrose into the diet with a physiological carbohydrate and lipid level (56 and 26% of total amount of calories, respectively) was accompanied by elevation of beta-lipoprotein level and an increase in the total cholesterol/phospholipid ratio.     

Intestinal lipoprotein synthesis. Comparison of nascent Golgi lipoproteins from chow-fed and hypercholesterolemic rats

Hypercholesterolemia, induced by a cholesterol-enriched diet, is associated with distinctive modifications in the serum lipoproteins of a variety of species. Present in the serum of these animals are several classes of lipoproteins enriched in cholesteryl esters and apolipoprotein E. To investigate the role of intestinal lipoprotein synthesis in diet-induced hypercholesterolemia, we characterized nascent lipoproteins retrieved from Golgi apparatus-rich fractions of intestinal epithelial cells from chow-fed control and hypercholesterolemic rats. To eliminate chylomicrons from the preparations, rats were fasted overnight prior to the experiments. Golgi very low density lipoproteins (d less than 1.006 g/ml) from control rats were triglyceride-rich lipoproteins that migrated slightly slower than pre-beta migrating serum very low density lipoproteins. These particles contained apoproteins B-240, A-IV, and A-I. Golgi very low density lipoproteins from hypercholesterolemic rats were likewise triglyceride-rich lipoproteins migrating electrophoretically like control Golgi very low density lipoproteins and they contained apoproteins B-240, A-IV, and A-I. However, these latter particles contained less triglyceride and more cholesterol compared to control Golgi very low density lipoproteins. In addition, by radioisotope incorporation studies, Golgi very low density lipoproteins from hypercholesterolemic rats contained relatively more apoprotein A-IV (21.6 vs. 11.0%) and less apoprotein B-240 (17.0 vs. 27.0%) than found in control Golgi very low density lipoproteins. Approximately 60% of the total apoprotein radioactivity was found in apoprotein A-I in both preparations. We conclude that intestinal lipoprotein synthesis is modified by diet-induced hypercholesterolemia. The significance of these modifications with respect to the marked hypercholesterolemia observed in these animals remains to be determined.     

Effect of Dietary Composition on Lipids in Serum and in Liver of Rats Fed a Cystine-excess Diet

The effects of dietary composition on lipids in serum and in liver of rats fed with a cystine- excess diet were investigated.

When starch was used as the carbohydrate source, the addition of excess-cystine caused an increase in serum cholesterol and phospholipids, and hepatomegaly. Phospholipids in serum of rats fed with a cystine-excess diet containing 5% corn oil were higher than those with a cystine-excess diet that was low in corn oil (0.1 %). The addition of konjac mannan and pectin prevented hypercholesterolemia, and the rise in phospholipids in serum was prevented by the addition of konjac mannan.

Liver cholesterol (mg/liver/100 g of body wt.) increased in rats fed with a cystine-excess diet.

The addition of excess cystine to a diet containing sucrose as the carbohydrate source resulted in a marked increase of cholesterol in serum and liver, and a decrease of serum triglycerides.

The replacement of starch by sucrose in the cystine-excess diet increased liver cholesterol.

Lipids, cholesterol, phospholipids and triglycerides in the liver, but not phospholipids, when expressed as mg per g of liver for rats fed with the diets containing sucrose, increased when compared to those for rats fed with the diets containing starch. In contrast, serum triglycerides increased.     

Cholesterol-free diet with a high ratio of polyunsaturated to saturated fatty acids in heterozygous familial hypercholesterolemia: significant lowering effect on plasma cholesterol

We have studied the effect of diet therapy on plasma lipoprotein metabolism in heterozygous familial hypercholesterolemia. Seven patients with a mean plasma cholesterol concentration of 323 +/- 67 mg/dl were hospitalized and kept on a cholesterol-free diet for as long as 11 days without any medication. The content of dietary cholesterol was approximately 1.4 mg a day, and dietary fat, carbohydrate and protein comprised 18.0, 69.2 and 12.8% of calories, respectively. The ratio of polyunsaturated to saturated fatty acids (P/S) was 3.1. At the end of the study period, plasma cholesterol was lowered by 14.2%, from 323 to 277 mg/dl, and low density lipoprotein (LDL) cholesterol by 17.5% from 229 to 189 mg/dl. Using density gradient ultracentrifugation, the major change in LDL cholesterol was found to be in those fractions with a mean density between 1.034 and 1.042, where cholesterol concentrations decreased from 132 to 87 mg/dl (34%). These results indicate that diet therapy with free-cholesterol and a high ratio of P/S is highly effective in controlling plasma cholesterol levels in heterozygous familial hypercholesterolemia.     

Cholesterol metabolism in the genetically hypercholesterolemic (RICO) rat. II. A study of plasma lipoproteins and effect of dietary cholesterol

The high plasma cholesterol concentration of the genetically hypercholesterolemic RICO rats fed a low cholesterol base diet (1.28 mg/ml) compared to that of SW rats (0.73 mg/ml) results from an increase in the cholesterol content of the d greater than or equal to 1.006 lipoproteins. Since the composition of each type of lipoprotein is similar in the two groups of rats, the RICO rat, therefore, is hyperlipoproteinemic with an increase in the number of lipoprotein particles, except VLDL and chylomicrons. Furthermore, the apolipoprotein E (apoE) content in the d less than or equal to 1.063 lipoproteins is higher in RICO than in SW rats, while that of apoA-I in HDL is lower. In rats fed 0.5% cholesterol base diet, cholesterolemia doubles in the two groups (SWCH, 1.32 +/- 0.10 mg/ml; RICOCH, 2.10 +/- 0.09 mg/ml). This hypercholesterolemia is due to an increased cholesterol content in VLDL and chylomicrons. These lipoproteins carry 60% (in SWCH) and 45% (in RICOCH) of the plasma cholesterol and are cholesterol-enriched compared with the lipoproteins observed in rats fed the base diet. In RICOCH, 24% of the plasma cholesterol is found in apoE-rich LDL2 (1.040 less than or equal to d less than or equal to 1.063), whereas in SWCH, this fraction contains only 11% of the plasma cholesterol. Finally, as before with the base diet, RICOCH shows an apoE enrichment of the d less than or equal to 1.063 lipoproteins and an apoA-I depletion of HDL compared to SWCH. These data suggest that hypercholesterolemia of the RICO rats results from a modification in the turnover of apoE-containing lipoproteins.     

Compensatory and adaptive changes in the small intestine and liver of rabbits after short-term cholesterol diet

Functional and morphological changes in the intestinal wall and liver were studied in rabbits on short-term cholesterol diet. It was established that with a rapid increase of cholesterol concentration in the general blood flow, the synthesis of high density lipoproteins in the intestinal wall was intensified. Enhanced hepatic elimination of cholesterol and chylomicrons from blood circulation contributes to cholesterol level stabilization in peripheral blood. With high density lipoprotein accumulation in the intestinal wall, cholesterol consumption did not change its concentration in the general blood flow. Structural changes in jejunal and liver mucosa were shown to depend on the degree of hypercholesterolemia and functional damage of these organs.     

Effects of protamine on blood lipoproteins in the early period of hypercholesterolemia in rabbits

The content of protein, cholesterol and triglycerides in chylomicrons and different classes of blood serum lipoproteins was studied under protamine action in early (1 month) hypercholesterolemia. Except the low density lipoproteins the amount of triglycerides in the particles studied was practically unchanged. The content of proteins in all classes of lipoproteins was greatly increased and this may indicate that protamine activates the blood lipoprotein system. The enrichment of lipoproteins with cholesterol may be taken as being a result of protamine action in early hypercholesterolemia. The peculiar feature in the effect of protamine on mentioned lipoprotein components was that the protein/cholesterol ratio didn't change in chylomicrons, decreased in very low density lipoproteins and low density lipoproteins and increased in high density lipoproteins as compared with controls.     

Morphine-induced alterations in plasma and tissue cholesterol levels

In rats fed a cholesterol-cholic acid supplemented diet, implantation of a 75 mg morphine pellet elevated total plasma cholesterol, raised low density lipoprotein (LDL) plus very low density lipoprotein (VLDL) cholesterol, and lowered high density lipoprotein (HDL) cholesterol levels. The resultant increase of the atherogenic index was accompanied by enhanced aortic cholesterol deposition. These alterations were prevented by daily administration of naltrexone (1.0 mg/kg, sc), and were not associated with hyperphagic or hepatotoxic actions of morphine. An increase in total plasma cholesterol and in LDL plus VLDL cholesterol was also observed in morphine pelleted rats maintained on a normal diet. The possible implications of opiate-induced hypercholesterolemia are discussed.     

Effects of cholestyramine on low density lipoprotein binding sites on liver membranes from rabbits with endogenous hypercholesterolemia induced by a wheat starch-casein diet

Rabbits fed a wheat starch-casein diet develop a marked hypercholesterolemia with a lipoprotein distribution similar to that of humans. Approximately 76% of the total cholesterol is carried in the low density lipoprotein (LDL) fraction (1.006 less than d less than 1.063 g/ml). Inclusion of 1% cholestyramine in the diet prevents the increase in plasma cholesterol. The cholestyramine effect is mediated through an increased fractional catabolic rate of 125I-LDL. In order to determine the potential role of hepatic LDL receptors in the removal of LDL from the plasma, binding of 125I-LDL and 125I-beta-VLDL (beta-migrating very low density lipoproteins) to hepatic membranes prepared from livers of rabbits fed the wheat starch-casein diet with or without cholestyramine supplementation was investigated. Membranes from livers of the cholestyramine-supplemented animals exhibit high levels of specific EDTA-sensitive binding of either of the 125I-labeled lipoproteins. Very little EDTA-sensitive binding occurs on liver membranes from wheat starch-casein-fed rabbits that have not been treated with cholestyramine. These results indicate that the hypercholesterolemia in rabbits associated with the wheat starch-casein diet is wholly or partially the result of a decreased number of specific hepatic LDL receptors and thus a decreased catabolism of plasma cholesterol. The response of the liver to the inclusion in the diet of the bile acid sequestrant, cholestyramine, is to maintain or increase the number of specific LDL binding sites, thus promoting catabolism of plasma cholesterol.     

Characterization of guinea pig plasma lipoproteins: the appearance of new lipoproteins in response to dietary cholesterol

Dietary cholesterol induces a hemolytic anemia in guinea pigs, accompanied by changes in the lipid composition of red cells and of plasma lipoproteins. This report presents a characterization of the lipoprotein species present in each main density class in both control and cholesterol-fed guinea pigs. Traces of a typical high density lipoprotein (HDL) were detected in control plasma. HDL from cholesterol-fed, anemic guinea pigs differed from control HDL in electron microscopic appearance and lipid and peptide composition. Long stacks of discs were observed in the electron microscope in addition to smaller, spherical particles characteristic of control HDL. Low density lipoproteins (LDL) from cholesterol-fed, anemic guinea pigs had two main populations, which were separated by gel chromatography. One population appeared in the electron microscope as large transparent discs and contained mainly unesterified cholesterol and phospholipids in a 2:1 molar ratio. The other population resembled control LDL in size and composition except for its high unesterified cholesterol content. Dietary cholesterol also altered the composition and decreased the electrophoretic mobility of very low density lipoproteins. Gel electrophoretic and immunochemical evidence indicates that a peptide (mol wt 35,000) appears in lipoproteins from cholesterol-fed, anemic guinea pigs that is undetectable in those of controls. Similarities between the cholesterol-induced lipoprotein abnormalities in guinea pigs and those reported in patients with obstructive jaundice, biliary cirrhosis, type III hyperlipoproteinemia, or familial lecithin:cholesterol acyltransferase deficiency are discussed.     

Effect of dietary carbohydrate type on lipoprotein lipase, hepatic lipase, and lecithin:cholesterol acyltransferase activities in cynomolgus monkeys

The effects of dietary sucrose and starch with and without exogenous cholesterol on postheparin plasma lipoprotein lipase (PHLA) and hepatic lipase (HLA) were studied in cynomolgus monkeys. Serum triglyceride levels were higher in sucrose-fed animals than starch and exogenous cholesterol lowered serum triglyceride levels when added to sucrose diet but not starch diets. Sucrose markedly increased insulin levels, more so than starch; however, dietary cholesterol lowered insulin levels in sucrose diet but increased the levels in starch diet. PHLA activity was increased two- to threefold greater in sucrose than in starch diets. Exogenous cholesterol lowered PHLA activity in sucrose diet but increased PHLA activity in starch diet. HLA activity was increased with sucrose more than starch. Lecithin:cholesterol acyltransferase (LCAT) activity was significantly higher in sucrose diets than in the starch diet. Addition of cholesterol to either of these diets lowered the LCAT activity. These results indicate that PHLA, HLA, and LCAT activities not only are affected by the nature of carbohydrates, but also are related to triglyceride metabolism. The interaction of carbohydrates and cholesterol in the diet by influencing these selected enzymes plays an integrated role in lipoprotein particle interconversion processes.     

Regulation of lipoprotein receptors on rat hepatomas in vivo

It has been shown previously that the rat hepatoma no. 7288C grown in vivo or in vitro expresses fewer receptors which recognize chylomicron remnants than does normal rat liver, and it was suggested that this may contribute to the deletion of dietary cholesterol-induced regulation of cholesterol synthesis in hepatomas (Barnard, G., Erickson, S. and Cooper, A. (1984) J. Clin. Invest. 74, 173-184). To investigate this further, Buffalo rats bearing hepatomas (HTC no. 7288C) were made hypercholesterolemic by feeding an atherogenic diet and hypocholesterolemic by ethinyl estradiol injections. Under all circumstances, tumor membranes had fewer receptors than liver membranes as measured by specific binding of [125I]chylomicron remnants. Ethinyl estradiol treatment increased the number of lipoprotein receptors 1.7-fold in liver membranes and 1.2-1.6-fold in tumor membranes, but hypercholesterolemia did not produce any significant changes in remnant binding to either liver or hepatoma membranes. Feeding an atherogenic diet induced a 2.4-fold increase in total cholesterol content in the liver, primarily as cholesterol ester; however, there was no change in total, free or ester cholesterol in the hepatomas. Acyl coenzyme A:cholesterol acyltransferase activity was low in this hepatoma line and neither treatment significantly affected its activity. One explanation for the lack of effect of the atherogenic diet on hepatoma cholesterol metabolism in addition to the decreased number of lipoprotein receptors might be the failure of access of lipoproteins to the tumor cell. To assess this, radioiodinated apo E-rich lipoproteins of various sizes were injected intravenously into rats with hepatomas. Their disappearance from the circulation was followed, and the uptake of each lipoprotein into a variety of tissues was determined. Chylomicron remnants were the most avidly removed particles. VLDLH, IDLH and HDLC were removed more slowly and less completely. None of the lipoproteins accumulated substantially in the tumors suggesting a limited access to the hepatoma tissue. Thus, in addition to the observed reduction in lipoprotein receptor number, limited lipoprotein access to the hepatoma tissue may be a significant factor in contributing to the apparent lack of feedback regulation of cholesterol synthesis by hepatoma tissue in vivo.     

Dietary saturated fatty acid content affects lymph lipoproteins: studies in the rat

We examined effects on intestinal absorption of cholesterol and triglycerides and intestinal lipoprotein formation by feeding rats diets in which saturated fatty acids (palmitic plus stearic) comprised 78%, 68%, 48%, or 38% of triglyceride fatty acids. Absorption into lymph of radiolabeled cholesterol was proportional to triglyceride absorption. The rates of absorption of these lipids were related inversely to the % saturated fatty acids fed. The distribution of newly absorbed cholesterol and triglyceride into intestinal lipoproteins differed. With increasing cholesterol absorption more was recovered in very low density lipoproteins in contrast to the appearance preferentially in chylomicrons of larger quantities of fatty acid. Lymph lipid content did not reflect a consistent pattern in relation to the experimental diet fed. The fatty acid composition of triglyceride-rich lymph lipoproteins resembled the diet closely. One-quarter of the intestinal lymph particles from rats fed the highly saturated diets was flattened and polygonal as judged by electron microscopy if cooled to room temperature; whereas with the same diets, particles collected and isolated at 37 degrees C were round. Proportions of A-I and C apolipoproteins in triglyceride-rich intestinal particles varied inversely; apoA-I increased as fat/cholesterol absorption was greater. Diet-induced alterations in plasma lipoproteins and increased circulating triglycerides in this study in rats were unrelated to the variations in intestinal absorption or lymph lipoprotein formation.     

Atherogenic hyperlipoproteinemia induced by cholesterol feeding the Patas monkey.

Patas monkeys were studied for 2 years on three dietary regimes: (1) commercial chow (control diet); (2) semipurified diet plus lard (fat-fed); and (3) semipurified diet plus lard and cholesterol (cholesterol-fed). The control and fat-fed animals had similar lipoproteins which were equivalent to the human very low density, low density (LDL), and high density lipoproteins. An additional lipoprotein referred to as LDL-II appeared to be equivalent to the human Lp(a). The cholesterol-fed animals developed accelerated atherosclerosis associated with a hypercholesterolemia which was characterized by (1) the appearance of beta-migrating lipoproteins (B=VLDL) in the d less than 1.006, (2) an increase in the intermediate lipoproteins and LDL, and (3) the appearance of LDL-II which contained a prominence of the arginine-rich apoprotein. The arginine-rich apoprotein was also a prominent component of the B-VLDL and intermediate lipoproteins. Characterization of this apoprotein revealed that it contained 11.5 mol % arginine, had a molecular weight of approximately 34 000, and coelectrophoresed with the arginine-rich apoprotein of man, dog, swine, rat, and rabbit.     

青春双歧杆菌对2型糖尿病模型大鼠肠道菌群和脂质代谢的影响

目的通过观察青春双歧杆菌对2型糖尿病模型大鼠肠道菌群的变化,和血清中总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL-C）、超氧化物歧化酶（SOD）和丙二醛（MDA）的水平,探讨青春双歧杆菌对2型糖尿病模型大鼠肠道功能和脂质代谢的影响。方法采用青春双歧杆菌灌胃2型糖尿病模型大鼠,取粪便检查正常菌群,取血和脏器检测TC、TG、HDL-C、SOD和MDA含量。结果青春双歧杆菌导致肠道内双歧杆菌、乳杆菌的数量增加,而肠杆菌、肠球菌数量下降;TC、TG和MDA水平下降,而HDL-C和SOD水平升高。结论青春双歧杆菌具有改善2型糖尿病模型大鼠肠道功能和降血脂作用,与二甲双胍联合应用效果更佳。     

Cholesterol and vitamins: revisited study

The link between low density lipoprotein and coronary heart disease has been widely studied. Oxidized LDL damages the artery wall, and a diet rich in vitamins and low in saturated fat and cholesterol may reduce this risk. Not only hypercholesterolemia but also low levels of high density lipoprotein cholesterol are critical risk factors for atherosclerosis and related diseases. It has been reported that high doses of B complex vitamin may be useful in lowering blood cholesterol and triglyceride levels in the body, however the use of this compound has been limited by an annoying flush and concern for toxicity. Niacin is a B-complex vitamin with anti-atherosclerotic properties and is an effective medication for raising high density lipoprotein. The combination of niacin with other lipid-lowering drugs, such as statins, reduces the dynamic of atherosclerosis disease. In addition, vitamin E is one of the most important lipid soluble anti-oxidants in humans, and reduces atherosclerosis plaque, coronary artery diseases and myocardial infarction. Vitamin E protects the integrity of membranes by inhibiting lipid peroxidation. In this study we revisited the interrelationship between cholesterol, low density lipoproteins and vitamins.     

Overexpressed lipoprotein lipase protects against atherosclerosis in apolipoprotein E knockout mice.

Lipoprotein lipase (LPL) is known to play a crucial role in lipoprotein metabolism by hydrolyzing triglycerides; however its role in atherogenesis has yet to be determined. We have previously shown that low density lipoprotein receptor knockout mice overexpressing LPL are resistant to diet-induced atherosclerosis due to the suppression of remnant lipoproteins. Plasma lipoproteins and atherosclerosis of apolipoprotein (apo) E knockout mice which overexpress the human LPL transgene (LPL/APOEKO) were compared with those of control apoE knockout mice (APOEKO). On a normal chow diet, LPL/APOEKO mice showed marked suppression of the plasma triglyceride levels compared with APOEKO mice (54 vs. 182 mg/dl), but no significant changes in plasma cholesterol and apoB levels. Non-high density lipoproteins (HDL) from LPL/APOEKO mice had lower triglyceride content, a smaller size, and a more positive charge compared with those from APOEKO mice. Cholesterol, apoA-I, and apoA-IV were increased in HDL. Although both groups developed hypercholesterolemia to a comparable degree in response to an atherogenic diet, the LPL/APOEKO mice developed 2-fold smaller fatty streak lesions in the aortic sinus compared to the APOEKO mice. In conclusion, overproduction of LPL is protective against atherosclerosis even in the absence of apoE.     

Increased risk of atherosclerosis by elevated plasma levels of phospholipid transfer protein

Plasma phospholipid transfer protein (PLTP) is thought to be involved in the remodeling of high density lipoproteins (HDL), which are atheroprotective. It is also involved in the metabolism of very low density lipoproteins (VLDL). Hence, PLTP is thought to be an important factor in lipoprotein metabolism and the development of atherosclerosis. We have overexpressed PLTP in mice heterozygous for the low density lipoprotein (LDL) receptor, a model for atherosclerosis. We show that increased PLTP activity results in a dose-dependent decrease in HDL, and a moderate stimulation of VLDL secretion (相似文献   

Tissue-specific knockouts of ACAT2 reveal that intestinal depletion is sufficient to prevent diet-induced cholesterol accumulation in the liver and blood

Acyl-CoA:cholesterol acyltransferase 2 (ACAT2) generates cholesterol esters (CE) for packaging into newly synthesized lipoproteins and thus is a major determinant of blood cholesterol levels. ACAT2 is expressed exclusively in the small intestine and liver, but the relative contributions of ACAT2 expression in these tissues to systemic cholesterol metabolism is unknown. We investigated whether CE derived from the intestine or liver would differentially affect hepatic and plasma cholesterol homeostasis. We generated liver-specific (ACAT2(L-/L-)) and intestine-specific (ACAT2(SI-/SI-)) ACAT2 knockout mice and studied dietary cholesterol-induced hepatic lipid accumulation and hypercholesterolemia. ACAT2(SI-/SI-) mice, in contrast to ACAT2(L-/L-) mice, had blunted cholesterol absorption. However, specific deletion of ACAT2 in the intestine generated essentially a phenocopy of the conditional knockout of ACAT2 in the liver, with reduced levels of plasma very low-density lipoprotein and hepatic CE, yet hepatic-free cholesterol does not build up after high cholesterol intake. ACAT2(L-/L-) and ACAT2(SI-/SI-) mice were equally protected from diet-induced hepatic CE accumulation and hypercholesterolemia. These results suggest that inhibition of intestinal or hepatic ACAT2 improves atherogenic hyperlipidemia and limits hepatic CE accumulation in mice and that depletion of intestinal ACAT2 is sufficient for most of the beneficial effects on cholesterol metabolism. Inhibitors of ACAT2 targeting either tissue likely would be beneficial for atheroprotection.