Type II Hyperlipoproteinemia159, 192 193 194 195 196 General Definitions By the Type II lipoprotein pattern we mean an increase in the concentration of lipoproteins that have discrete β mobility b

Fat Transport in Lipoproteins — An Integrated Approach to Mechanisms and Disorders

In healthy individuals, acute changes in cholesterol intake produce modest changes in plasma cholesterol levels. A striking exception occurs in sitosterolemia, an autosomal recessive disorder characterized by increased intestinal absorption and decreased biliary excretion of dietary sterols, hypercholesterolemia, and premature coronary atherosclerosis. We identified seven different mutations in two adjacent, oppositely oriented genes that encode new members of the adenosine triphosphate (ATP)-binding cassette (ABC) transporter family (six mutations in ABCG8 and one in ABCG5) in nine patients with sitosterolemia. The two genes are expressed at highest levels in liver and intestine and, in mice, cholesterol feeding up-regulates expressions of both genes. These data suggest that ABCG5 and ABCG8 normally cooperate to limit intestinal absorption and to promote biliary excretion of sterols, and that mutated forms of these transporters predispose to sterol accumulation and atherosclerosis.

https://science.sciencemag.org/content/sci/290/5497/1771.full.pdf

Accumulation of Dietary Cholesterol in Sitosterolemia Caused by Mutations in Adjacent ABC Transporters

To calculate the effect of changes in carbohydrate and fatty acid intake on serum lipid and lipoprotein levels, we reviewed 27 controlled trials published between 1970 and 1991 that met specific inclusion criteria. These studies yielded 65 data points, which were analyzed by multiple regression analysis using isocaloric exchanges of saturated (sat), monounsaturated (mono), and polyunsaturated (poly) fatty acids versus carbohydrates (carb) as the independent variables. For high density lipoprotein (HDL) we found the following equation: delta HDL cholesterol (mmol/l) = 0.012 x (carb----sat) + 0.009 x (carb----mono) + 0.007 x (carb---- poly) or, in milligrams per deciliter, 0.47 x (carb----sat) + 0.34 x (carb----mono) + 0.28 x (carb----poly). Expressions in parentheses denote the percentage of daily energy intake from carbohydrates that is replaced by saturated, cis-monounsaturated, or polyunsaturated fatty acids. All fatty acids elevated HDL cholesterol when substituted for carbohydrates, but the effect diminished with increasing unsaturation of the fatty acids. For low density lipoprotein (LDL) the equation was delta LDL cholesterol (mmol/l) = 0.033 x (carb----sat) - 0.006 x (carb----mono) - 0.014 x (carb----poly) or, in milligrams per deciliter, 1.28 x (carb----sat) - 0.24 x (carb----mono) - 0.55 x (carb---- poly). The coefficient for polyunsaturates was significantly different from zero, but that for monounsaturates was not. For triglycerides the equation was delta triglycerides (mmol/l) = -0.025 x (carb----sat) - 0.022 x (carb----mono) - 0.028 x (carb---- poly) or, in milligrams per deciliter, -2.22 x (carb----sat) - 1.99 x (carb----mono) - 2.47 x (carb----poly).(ABSTRACT TRUNCATED AT 250 WORDS)

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Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials.

OBJECTIVES: To re-state the principles underlying the Goldberg cut-off for identifying under-reporters of energy intake, re-examine the physiological principles and update the values to be substituted into the equation for calculating the cut-off, and to examine its use and limitations. RESULTS: New values are suggested for each element of the Goldberg equation. The physical activity level (PAL) for comparison with energy intake:basal metabolic rate (EI:BMR) should be selected to reflect the population under study; the PAL value of 1.55 x BMR is not necessarily the value of choice. The suggested value for average within-subject variation in energy intake is 23% (unchanged), but other sources of variation are increased in the light of new data. For within-subject variation in measured and estimated BMR, 4% and 8.5% respectively are suggested (previously 2.5% and 8%), and for total between-subject variation in PAL, the suggested value is 15% (previously 12.5%). The effect of these changes is to widen the confidence limits and reduce the sensitivity of the cut-off. CONCLUSIONS: The Goldberg cut-off can be used to evaluate the mean population bias in reported energy intake, but information on the activity or lifestyle of the population is needed to choose a suitable PAL energy requirement for comparison. Sensitivity for identifying under-reporters at the individual level is limited. In epidemiological studies information on home, leisure and occupational activity is essential in order to assign subjects to low, medium or high PAL levels before calculating the cut-offs. In small studies, it is desirable to measure energy expenditure, or to calculate individual energy requirements, and to compare energy intake directly with energy expenditure.

Critical evaluation of energy intake using the Goldberg cut-off for energy intake:basal metabolic rate. A practical guide to its calculation, use and limitations

Dietary influences on serum lipids and lipoproteins.

Quantitative isolation and gas–liquid chromatographic analysis of total fecal bile acids

Quantitative isolation and gas--liquid chromatographic analysis of total dietary and fecal neutral steroids.

The metabolism of beta-sitosterol was compared to that of cholesterol in 12 patients. Sterol balance methods were supplemented by radiosterol studies, with the following results. (a) Plasma concentrations of beta-sitosterol ranged from 0.30 to 1.02 mg/100 ml plasma in patients on intakes of beta-sitosterol typical of the American diet. Plasma levels were raised little when intakes were increased greatly, and on fixed intakes they were constant from week to week. On diets devoid of plant sterols, the plasma and feces rapidly became free of beta-sitosterol. (b) The percentage of esterified beta-sitosterol in the plasma was the same as for cholesterol. However, the rate of esterification of beta-sitosterol was slower than that for cholesterol. (c) Specific activity-time curves after simultaneous pulse labeling with beta-sitosterol-(3)H and cholesterol-(14)C conformed to two-pool models. The two exponential half-lives of beta-sitosterol were much shorter than for cholesterol, and pool sizes were much smaller. Values of turnover for beta-sitosterol obtained by the sterol balance method agreed closely with those derived by use of the two-pool model. There was no endogenous synthesis of beta-sitosterol in the patients studied; hence, daily turnover of beta-sitosterol equaled its daily absorption. Absorption of beta-sitosterol was 5% (or less) of daily intake, while cholesterol absorption ranged from 45 to 54% of intake. (d) About 20% of the absorbed beta-sitosterol was converted to cholic and chenodeoxycholic acids. The remainder was excreted in bile as free sterol; this excretion was more rapid than that of cholesterol. (e) The employment of beta-sitosterol as an internal standard to correct for losses of cholesterol in sterol balance studies is further validated by the results presented here.

/pdf/metabolism-of-beta-sitosterol-in-man-2eqk64edml.pdf

Metabolism of beta-sitosterol in man.

Studies were carried out to examine the effects of dietary fat and cholesterol on cholesterol homeostasis in man. 75 12-wk studies were carried out during intake of 35% of calories as either saturated or polyunsaturated fat, first low and then high in dietary cholesterol. Dietary fat and cholesterol intakes, plasma lipid and lipoprotein levels, cholesterol absorption and sterol synthesis in isolated blood mononuclear leukocytes were measured during each diet period. In 69% of the studies the subjects compensated for the increased cholesterol intake by decreasing cholesterol fractional absorption and/or endogenous cholesterol synthesis. When an increase in plasma cholesterol levels was observed there was a failure to suppress endogenous cholesterol synthesis. Plasma cholesterol levels were more sensitive to dietary fat quality than to cholesterol quantity. The results demonstrate that the responses to dietary cholesterol and fat are highly individualized and that most individuals have effective feedback control mechanisms.

/pdf/heterogeneity-of-cholesterol-homeostasis-in-man-response-to-33iqw9ibbf.pdf

Heterogeneity of cholesterol homeostasis in man. Response to changes in dietary fat quality and cholesterol quantity.

Cholesterol balance studies were carried out in 11 patients with various types of hyperlipoproteinemia to determine the mechanism by which unsaturated fats lower plasma cholesterol. Unsaturated fats produced no increase in fecal endogenous neutral steroids in 10 of 11 patients and no decrease in absorption of exogenous cholesterol in 5 patients who received cholesterol in the diet. In 8 of 11 patients no changes occurred in excretion of bile acids during the period on unsaturated fat when plasma cholesterol was declining. However, in 3 of 11 patients small but significant increases in bile acid excretion were found during this transitional period; in 2 others increases also occurred after plasma cholesterol had become constant at lower levels on unsaturated fat.Since the majority of patients showed no change in cholesterol or bile acid excretions during the transitional period, we propose that when excretion changes did occur they were probably not the cause of the plasma cholesterol change. Furthermore, turnover data and specific activity curves suggested that cholesterol synthesis was not influenced by exchange of dietary fats. Thus, excluding changes in excretion and synthesis, we conclude that it is most likely that unsaturated fats cause plasma cholesterol to be redistributed into tissue pools. We have also examined the possibility that cholesterol which is redistributed into tissues could be secondarily excreted as neutral steroids or bile acids. In at least 5 of 11 patients excretion patterns were consistent with this explanation. However, we cannot rule out that excretion changes may have been due to alterations in transit time, to changes in bacterial flora, or to transitory changes in absorption or synthesis of cholesterol or bile acids. Our conclusion that unsaturated fats cause a redistribution of cholesterol between plasma and tissue pools points to the necessity in future to explore where cholesterol is stored, to what extent stored cholesterol can be mobilized, and to define the factors governing these fluxes.

/pdf/the-effects-of-unsaturated-dietary-fats-on-absorption-3c7k92uew5.pdf

E. H. Ahrens

Papers

Quantitative isolation and gas–liquid chromatographic analysis of total fecal bile acids

Quantitative isolation and gas--liquid chromatographic analysis of total dietary and fecal neutral steroids.

Metabolism of beta-sitosterol in man.

Heterogeneity of cholesterol homeostasis in man. Response to changes in dietary fat quality and cholesterol quantity.

The effects of unsaturated dietary fats on absorption, excretion, synthesis, and distribution of cholesterol in man