Dietary Cholesterol Inhibits Whole-Body but Not Cerebrum Cholesterol Synthesis In Young Pigs

The purpose of the present study was to estimate whole-body fatty acid and cholesterol synthesis in weight-stable adults and to determine the likely effect on the doubly-labelled water (DLW) method for measuring energy expenditure. Synthesis was measured by 2H incorporation over 14 d in six adult males in approximate energy balance following noradrenaline infusion to maximize mobilization of free fatty acid from adipose tissue. The inter-individual variation in synthesis rates was large and in one subject the proportion of free fatty acid synthesized was ten times that of the mean of the rest of the group; the fasting concentration of esterified fatty acid in this subject was five times that of the rest of the group indicating likely violation of the assumptions underlying the calculation of whole-body synthesis. After 14 d of labelling in the other five subjects, 0·9 (SEM 0·3) % OF THE CIRCULATING FREE FATTY ACID, 9·3 (sem 3·0) % of the esterified fatty acid, 14·6 (sem 2·4) % of the free cholesterol and 28·3 (sem 3·7) % of esterified cholesterol had been synthesized de novo. A high rate of synthesis correlated with a low pre-dose 2H abundance both within and between lipid classes suggesting that natural 2H abundance variations in some lipid classes may be used to determine their metabolic origin. Whole-body synthetic rates were 8 g/d for fatty acid and 0·3–0·5 g/d for cholesterol. These values correspond to very small errors on DLW-derived estimates of CO2 production; -2·5 litres/d for fatty acid and -0·1 to -0·2 litres/d for cholesterol. These results, obtained in subjects typically consuming a diet with a lower fat and cholesterol content that the typical Western diet, suggest that the DLW method is unlikely to be affected by fatty acid and cholesterol synthesis in subjects in energy balance consuming a typical Western diet.

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Effects of dietary cholesterol and fat on serum non-cholesterol sterols according to different apolipoprotein E subgroups among healthy men

British Journal Of Nutrition ◽

10.1017/s0007114508894330 ◽

2008 ◽

Vol 100 (2) ◽

pp. 373-379 ◽

Cited By ~ 5

Author(s):

Markku J. Nissinen ◽

Helena Gylling ◽

Tatu A. Miettinen

Keyword(s):

Cholesterol Synthesis ◽

Cholesterol Metabolism ◽

Dietary Cholesterol ◽

Serum Levels ◽

High Cholesterol ◽

High Fat ◽

Low Fat ◽

Apo E ◽

The Impact ◽

Low Cholesterol

The impact of apo E phenotypes on applicability of relative cholesterol synthesis (lathosterol:cholesterol) and absorption (ratios of cholestanol, campesterol and sitosterol to cholesterol) during diets of various cholesterol and fat content is unclear. We examined and compared with each other both relative and absolute synthesis and absorption among twenty-nine men, of whom eight, nine and twelve had apo E phenotypes 2 (2/2, 2/3, 2/4), 3 (3/3) and 4 (3/4, 4/4), respectively. Serum lipids, lipoproteins, sterols and cholesterol metabolism were examined on four subsequent diets: high-cholesterol high-fat (home diet; HD), low-cholesterol low-fat (LCLF), high-cholesterol low-fat (HCLF) and low-cholesterol high-fat (LCHF). LDL-cholesterol (LDL-C) level was about 40 % lower (P < 0·05) in apo E2 than apo E3 and E4 groups irrespective of dietary fat and cholesterol. Serum proportions of phytosterols were determined apo E-dependently on LCLF and HCLF, and those of lathosterol, cholestanol and campesterol were increased in apo E2 and E3 groups (P < 0·05 for each v. HD). Serum proportion of sitosterol reflected almost consistently apo E phenotype (r range+0·308 to+0·383; P range 0·214–0·011). Relative cholesterol synthesis and absorption reflected respective absolute values during each diet in the apo E4 group (r range+0·713 to+0·893; P < 0·05 for each), but only during HD (r+0·594; P = 0·015) in the apo E2+E3 group. The consumption of a high amount of fat did not interfere with cholesterol metabolism or serum levels of LDL-C differently in apo E phenotypes. Surrogate sterol markers of cholesterol metabolism reflected absolute ones (especially in the apo E4 group) and apo E phenotypes despite variable amounts of dietary cholesterol and fat.

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Plasma Non-cholesterol Sterols as Markers of Cholesterol Synthesis and Intestinal Absorption: A Critical Review

Current Pharmaceutical Design ◽

10.2174/1381612826666200730220230 ◽

2020 ◽

Vol 26 (40) ◽

pp. 5152-5162

Author(s):

Eder Carlos Rocha Quintão

Keyword(s):

Intestinal Absorption ◽

Cholesterol Synthesis ◽

Cholesterol Metabolism ◽

Plasma Concentrations ◽

Cholesterol Absorption ◽

Population Based ◽

Whole Body ◽

Intestinal Lumen ◽

Intestinal Cholesterol Absorption ◽

Artery Disease

Plasma concentrations of phytosterols and non-cholesterol sterol precursors of cholesterol synthesis have been used as markers of intestinal cholesterol absorption and synthesis in inherited and secondary dyslipidemias and in population-based investigations to evaluate the risk for cardiovascular disease, respectively. The method aims at replacing initial research procedures such as the use of stable isotopes associated with fecal steroid balance, which are limited by the high cost and tedious procedures. However, we show in this review that numerous results obtained with serum sterol measurements are contradictory. In this regard, the following points are discussed: 1) how phytosterols relate to atherosclerosis considering that defects in biliary output or in the transport of phytosterols from the intestinal mucosa back into the intestinal lumen provide increased content of phytosterols and other sterols in plasma and tissues, thus not allowing to conclude that their presence in arteries and atheromas represents the etiology of atherosclerosis; 2) serum non-cholesterol sterols as markers of cholesterol synthesis and absorption, such as cholestanol, present discrepant results, rendering them often inadequate to identify cases of coronary artery disease as well as alterations in the whole body cholesterol metabolism; 3) such methods of measurement of cholesterol metabolism are confounded by factors like diabetes mellitus, body weight and other pathologies including considerable hereditary hyperlipidemias biological variabilities that influence the efficiency of synthesis and intestinal absorption of cholesterol.

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Absorption and metabolism of cholesterol in familial hypercholesterolemia

Clinical Science ◽

10.1042/cs0760297 ◽

1989 ◽

Vol 76 (3) ◽

pp. 297-301 ◽

Cited By ~ 8

Author(s):

Helena Gylling ◽

Tatu A. Miettinen

Keyword(s):

Cholesterol Synthesis ◽

Familial Hypercholesterolaemia ◽

Cholesterol Metabolism ◽

Low Density Lipoprotein ◽

Dietary Cholesterol ◽

Density Lipoprotein ◽

Cholesterol Absorption ◽

Lipoprotein Cholesterol ◽

Low Density ◽

Cholesterol Intake

1. The present study investigated the role of intestinal cholesterol absorption in the regulation of cholesterol metabolism and serum lipoprotein levels in 22 patients with heterozygous familial hypercholesterolaemia on low to normal cholesterol intake. 2. The results showed that the higher the dietary cholesterol absorption, the lower was the overall synthesis of cholesterol. Efficient cholesterol absorption actually reduced the elimination of cholesterol as faecal neutral sterols but not consistently as bile acids. 3. In multifactorial analysis, body mass index and dietary plant sterols were negatively associated with cholesterol absorption, but were unrelated to cholesterol synthesis. 4. Fractional cholesterol absorption was related only to the serum very-low-density triacylglycerol level. It was not associated with the total or low-density lipoprotein cholesterol levels. On the other hand, cholesterol synthesis was significantly associated with the serum concentrations of very-low-density lipoprotein and intermediate-density lipoprotein cholesterol and triacylglycerols, and with those of low-density lipoprotein triacylglycerols. 5. In conclusion, dietary cholesterol absorption is an essential regulator of cholesterol homoeostasis in familial hypercholesterolaemia, even in patients on low cholesterol intake.

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Measurement of endogenous synthesis of plasma cholesterol in rats and humans using MIDA

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1993.264.1.e136 ◽

1993 ◽

Vol 264 (1) ◽

pp. E136-E147 ◽

Cited By ~ 6

Author(s):

R. A. Neese ◽

D. Faix ◽

C. Kletke ◽

K. Wu ◽

A. C. Wang ◽

...

Keyword(s):

Free Cholesterol ◽

Cholesterol Synthesis ◽

Plasma Cholesterol ◽

Charge Ratio ◽

Whole Body ◽

Distribution Analysis ◽

Normal Women ◽

Endogenous Cholesterol ◽

Endogenous Synthesis

We used the mass isotopomer distribution analysis (MIDA) technique to measure endogenous synthesis of plasma cholesterol in vivo in rats and normal human subjects. Sodium [1-13C]- or [2-13C]acetate was infused, and plasma free cholesterol was analyzed by gas chromatography-mass spectrometry. Frequencies of mass isotopomers M0-M4 (mass-to-charge ratio 368-372) were quantified. The enrichment of the true precursor for cholesterol synthesis (acetyl-coenzyme A in contributing tissues) was determined using the MIDA method. This technique remains mathematically valid even if more than one tissue contributes to circulating free cholesterol. The fractional contribution (f) from endogenous synthesis to free cholesterol in normal women (n = 5) was 2.48 +/- 0.39% after 7 h in the postabsorptive state and 1.27 +/- 0.41% after 8 h of refeeding. In ad libitum-fed rats (n = 12), f was 2.89 +/- 0.44% after 12 h, whereas administration of recombinant tumor necrosis factor increased this value fourfold. Next, the rate constant (k) for removal of labeled free cholesterol from plasma was calculated. Higher masses (M2-M4) were followed to avoid the problem of persistent label incorporation. During the 60 h after cessation of [13C]acetate infusions, k was 0.02490 +/- 0.00298/h in humans. Using these values of k and f, absolute cholesterogenesis was 568 +/- 55 mg/day in normal women (follicular menstrual phase), similar to prior estimates based on whole body sterol balances. Women also exhibited a diurnal variation for endogenous cholesterol synthesis (34.6 +/- 5.4 mg/h nighttime vs. 15.9 +/- 5.2 mg/h daytime) consistent with current knowledge about rhythms in cholesterogenesis. Checks on the model were internally consistent (e.g., comparisons among different isotopomers for calculating precursor enrichment). We conclude that fractional and absolute endogenous cholesterol synthesis can be measured using stable isotopes in vivo by the MIDA technique.

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