Several nuclear hormone receptors involved in lipid metabolism form obligate heterodimers with retinoid X receptors (RXRs) and are activated by RXR agonists such as rexinoids. Animals treated with rexinoids exhibited marked changes in cholesterol balance, including inhibition of cholesterol absorption and repressed bile acid synthesis. Studies with receptor-selective agonists revealed that oxysterol receptors (LXRs) and the bile acid receptor (FXR) are the RXR heterodimeric partners that mediate these effects by regulating expression of the reverse cholesterol transporter, ABC1, and the rate-limiting enzyme of bile acid synthesis, CYP7A1, respectively. Thus, these RXR heterodimers serve as key regulators of cholesterol homeostasis by governing reverse cholesterol transport from peripheral tissues, bile acid synthesis in liver, and cholesterol absorption in intestine.

https://science.sciencemag.org/content/sci/289/5484/1524.full.pdf

Regulation of Absorption and ABC1-Mediated Efflux of Cholesterol by RXR Heterodimers

Oxygenated derivatives of cholesterol (oxysterols) present a remarkably diverse profile of biological activities, including effects on sphingolipid metabolism, platelet aggregation, apoptosis, and ...

Oxysterols: modulators of cholesterol metabolism and other processes.

Objective. —To examine prospectively the relationship between dietary fiber and risk of coronary heart disease. Design. —Cohort study. Setting. —In 1986, a total of 43 757 US male health professionals 40 to 75 years of age and free from diagnosed cardiovascular disease and diabetes completed a detailed 131 -item dietary questionnaire used to measure usual intake of total dietary fiber and specific food sources of fiber. Main Outcome Measure. —Fatal and nonfatal myocardial infarction (Ml). Results. —During 6 years of follow-up, we documented 734 cases of Ml (229 were fatal coronary heart disease). The age-adjusted relative risk (RR) for total Ml was 0.59 (95% confidence interval [CI], 0.46 to 0.76) among men in the highest quintile of total dietary fiber intake (median, 28.9 g/d) compared with men in the lowest quartile (median, 12.4 g/d). The inverse association was strongest for fatal coronary disease (RR, 0.45; 95% CI, 0.28 to 0.72). After controlling for smoking, physical activity and other known nondietary cardiovascular risk factors, dietary saturated fat, vitamin E, total energy intake, and alcohol intake, the RRs were only modestly attenuated. A 10-g increase in total dietary fiber corresponded to an RR for total Ml of 0.81 (95% CI, 0.70 to 0.93). Within the three main food contributors to total fiber intake (vegetable, fruit, and cereal), cereal fiber was most strongly associated with a reduced risk of total Ml (RR, 071; 95% CI, 0.55 to 0.91 for each 10-g increase in cereal fiber per day). Conclusions. —Our results suggest an inverse association between fiber intake and Ml. These results support current national dietary guidelines to increase dietary fiber intake and suggest that fiber, independent of fat intake, is an important dietary component for the prevention of coronary disease. (JAMA. 1996;275:447-451)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=jama&articleId=396216&pdfFileName=jama_275_6_036.pdf

Vegetable, Fruit, and Cereal Fiber Intake and Risk of Coronary Heart Disease Among Men

Background Dietary plant sterols, especially sitostanol, reduce serum cholesterol by inhibiting cholesterol absorption. Soluble sitostanol may be more effective than a less soluble preparation. We tested the tolerability and cholesterol-lowering effect of margarine containing sitostanol ester in a population with mild hypercholesterolemia. Methods We conducted a one-year, randomized, double-blind study in 153 randomly selected subjects with mild hypercholesterolemia. Fifty-one consumed margarine without sitostanol ester (the control group), and 102 consumed margarine containing sitostanol ester (1.8 or 2.6 g of sitostanol per day). Results The margarine containing sitostanol ester was well tolerated. The mean one-year reduction in serum cholesterol was 10.2 percent in the sitostanol group, as compared with an increase of 0.1 percent in the control group. The difference in the change in serum cholesterol concentration between the two groups was -24 mg per deciliter (95 percent confidence interval, -17 to -...

https://www.nejm.org/doi/pdf/10.1056/NEJM199511163332002

Reduction of serum cholesterol with sitostanol-ester margarine in a mildly hypercholesterolemic population

bkground.— Although dietary factors are suspected to be important determinants of coronary heart disease (CHD) risk, the direct evidence is relative-lse. Methods.— The Adventist Health Study is a prospective cohort investigation of 31 208 non-Hispanic white California Seventh-Day Adventists. Extensive dietary information was obtained at baseline, along with the values of traditional coronary risk factors. These were related to risk of definite fatal CHD or definite nonfatal- dial infarction. Results.— Subjects who consumed nuts frequently (more than four times per week) experienced substantially fewer definite fatal CHD events (relative risk, 0.52; 95% confidence interval [CI], 0.36 to 0.76) and definite nonfatal myocardial infarctions (relative risk, 0.49; 95% CI, 0.28 to 0.85), when compared with those who consumed nuts less than once per week. These findings persisted on covariate adjustment and were seen in almost all of 16 different subgroups of the population. Subjects who usually consumed whole wheat bread also experienced lower rates of definite nonfatal myocardial infarction (relative risk, 0.56; 95% CI, 0.35 to 0.89) and definite fatal CHD (relative risk, 0.89; 95% CI, 0.60 to 1.33) when compared with those who usually ate white bread. Men who ate beef at least three times each week had a higher risk of definite fatal CHD (relative risk, 2.31; 95% CI, 1.11 to 4.78), but this effect was not seen in women or for the nonfatal myocardial infarction end point. Conclusion.— Our data strongly suggest that the frequent consumption of nuts may protect against risk of CHD events. The favorable fatty acid profile of many nuts is one possible explanation for such an effect. (Arch Intern Med. 1992;152:1416-1424)

https://espace.library.uq.edu.au/view/UQ:260481/UQ260481_fulltext.pdf

A possible protective effect of nut consumption on risk of coronary heart disease. The Adventist Health Study.

Inhibition of cholesterol absorption in rats by plant sterols.

Mixed micelles were prepared containing combinations of either taurocholate or taurochenodeoxycholate, monoolein, oleic acid, dioleylphosphatidylcholine (lecithin) and cholesterol. These were incubated with commercial bile-acid-sequestering resins, cholestyramine and DEAE-Sephadex, or various dietary fibers and fiber components including wheat bran, cellulose, alfalfa, lignin and 2 viscosity grades of guar gum. Binding was determined as the difference between the radioactivity of each micellar component added and that recovered in the centrifugal supernatant after incubation. In general, the extent of bile salt sequestration was characteristic and reproducible for each bile salt, and was largely unaffected by the presence of one or more additional components of the micellar mixture, including the other bile salt. Cholestyramine bound 81-92% of the bile salts and 86-99% of the phospholipid and cholesterol present in micelles. DEAE-Sephadex sequestered only 49% of the taurocholate and 84% of the taurochenodeoxycholate, but completely removed all of the phospholipid and cholesterol from micelles containing either bile salt. Among the dietary fibers, guar gum of either viscosity bound between 20-38% of each micellar component, whereas lignin, alfalfa, wheat bran and cellulose were progressively less effective in sequestration of individual components of mixed micelles. The extent of sequestration of micellar components by these resins and fibers is reasonably correlated with the effects of these same materials on lymphatic absorption of lipids and to their suggested hypocholesteremic properties.

L L Gallo

Papers

Inhibition of cholesterol absorption in rats by plant sterols.

Dietary fibers: V. Binding of bile salts, phospholipids and cholesterol from mixed micelles by bile acid sequestrants and dietary fibers.

Cholesterol absorption in rat intestine: role of cholesterol esterase and acyl coenzyme A:cholesterol acyltransferase

Discrimination between cholesterol and sitosterol for absorption in rats

Dietary fibers III. Effects of chronic intake on cholesterol absorption and metabolism in the rat