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Background: In utero exposure to excessive cholesterol has been shown to increase fetal plasma cholesterol concentration and predispose adult offspring to cardiovascular disease (CVD) risk. Because lipid-lowering drugs are contraindicated during pregnancy, natural cholesterol-lowering compounds may be a safe and effective alternative to reduce CVD risk in offspring born to hypercholesterolemic mothers. Objective: This study used the hypercholesterolemic apolipoprotein E-deficient (apoE-/-) mouse model to test the hypothesis that mothers supplemented with phytosterols during gestation and lactation would produce offspring with a more favorable lipid profile than offspring from unsupplemented mothers, despite having a genetic predisposition toward hypercholesterolemia. Methods: Sixteen female apoE-/- mice were randomly assigned to 2 diets fed throughout the gestation and lactation periods: a cholesterol-enriched diet (CH) (0.15%) or the cholesterol-enriched diet supplemented with phytosterols (CH/PS) (2%). Serum lipids and lipoproteins were measured by enzyme assay and nuclear magnetic resonance spectroscopy, respectively, and liver cholesterol was analyzed by GC. Results: Compared with the CH-fed dams at the end of lactation, phytosterol-supplemented dams displayed lower (P< 0.05) serum total cholesterol (-55%), non-HDL cholesterol (-56%), and LDL cholesterol (-47%), but no change (P> 0.05) in HDL cholesterol and triacylglycerol (TG) concentrations. Pups from phytosterol-fed dams demonstrated lower (P< 0.05) total cholesterol (-25%), non-HDL cholesterol (-25%), LDL cholesterol (-47%), and TGs (-41 %), without any change (P> 0.05) in HDL cholesterol compared with pups from CH-fed dams. Furthermore, compared with pups from CH-fed dams, pups from phytosterol-supplemented dams displayed a lower (P< 0.05) number of total LDL particles (-34%), VLDL particles (-31 %), and HDL particles (-30%). Conclusion: Our results in apoE-/- mice suggest that even under strong genetic predisposition to hypercholesterolemia, pups born to mothers supplemented with phytosterols during gestation and lactation exhibit favorable liver and serum lipid responses compared with pups from unsupplemented mothers. [ABSTRACT FROM AUTHOR]

The effect of dietary plant sterols on cholesterol homeostasis has been well characterized in the intestine, but how plant sterols affect lipid metabolism in other lipid-rich tissues is not known. Changes in hepatic cholesterol homeostasis in response to high dietary intakes of plant sterols were determined in male golden Syrian hamsters fed hypercholesterolemia-inducing diets with and without 2% plant sterols (wt:wt; Reducol, Forbes Meditech) for 28 d. Plasma and hepatic cholesterol concentrations, cholesterol biosynthesis and absorption, and changes in the expression of sterol response element binding protein 2 (SREBP2) and liver X receptor-beta (LXRbeta) and their target genes were measured. Plant sterol feeding reduced plasma total cholesterol, non-HDL cholesterol, and HDL cholesterol concentrations 43% (P < 0.0001), 60% (P < 0.0001), and 21% (P = 0.001), respectively, compared with controls. Furthermore, there was a 93% reduction (P < 0.0001) in hepatic total cholesterol and >6-fold (P = 0.029) and >2-fold (P < 0.0001) increases in hepatic beta-sitosterol and campesterol concentrations, respectively, in plant sterol-fed hamsters compared with controls. Plant sterol feeding also increased fractional cholesterol synthesis >2-fold (P < 0.03) and decreased cholesterol absorption 83% (P < 0.0001) compared with controls. Plant sterol feeding increased hepatic protein expression of cytosolic (inactive) SREBP2, decreased nuclear (active) SREBP2, and tended to increase LXRbeta (P = 0.06) and ATP binding cassette transporter G5, indicating a differential modulation of the expression of proteins central to cholesterol metabolism. In conclusion, high-dose plant sterol feeding of hamsters changes hepatic protein abundance in favor of cholesterol excretion despite lower hepatic cholesterol concentrations and higher cholesterol fractional synthesis. [ABSTRACT FROM AUTHOR]

To gain insight into the regulation of hepatic sterol-responsive genes that are thought to mediate the hypocholesterolemic effects of guar gum (GG) consumption, the mRNA and protein expression of sterol regulatory element binding protein 2 (SREBP2), LDL receptor (LDLr), and scavenger receptor class B, type 1 (SR-B1) were examined in pigs consuming an atherogenic control diet or the control diet supplemented with 10% GG. Compared with the control group, GG consumption reduced (P < 0.05) plasma total cholesterol and LDL cholesterol concentrations by 27 and 37%, respectively. Furthermore, hepatic free cholesterol concentration was lower (P < 0.05) in the GG-fed pigs in comparison with the control group. GG consumption increased hepatic LDLr mRNA (1.5-fold of the control, P = 0.09) and protein (2-fold of the control, P < 0.05) expression in comparison with the control group. However, GG consumption reduced hepatic SR-B1 mRNA to 36% of the control (P < 0.05) expression but did not affect (P = 0.19) SR-B1 protein abundance in comparison with the control group. Although SREBP2 mRNA expression was similar (P = 0.89) in the 2 groups, GG consumption increased (P < 0.05) the expression of the cytoplasmic precursor (3-fold of the control) and nuclear active forms (1.5-fold of the control) of SREBP2. We conclude that the hypocholesterolemic effects of GG consumption are related to a reduction in hepatic free cholesterol concentration and associated increases in nuclear active SREBP2 expression and hepatic LDLr abundance. [ABSTRACT FROM AUTHOR]

Diacyiglycerol (DAG) may undergo differential metabolism compared with triacylglycerol (TAG) in humans, possibly resulting in decreased serum TAG concentration and TAG synthesis and increased energy expenditure (EEl, thus reducing fat accumulation. Our objective was to examine the efficacy of DAG oil )Enova oil) consumption on serum lipid profiles, hepatic lipogenesis, EE, and body weight and composition compared with a control oil-blend composed of sunflower, safflower, and rapeseed oils at a 1:1:1 ratio. Twenty-six overweight (78.3 ± 3.6 kg body weight and BM) 30.0 ± 0.7 kg/rn2) mildly hypertriglyceridemic 11.81 ± 0.66 rnmol/L) women underwent 2 treatment phases of 28 d separated by a 4-wk washout period using a randomized crossover design. They consumed 40 g/d of either DAG or control oil during treatment phases. The baseline, EE, fat oxidation, body composition, and lipid profiles did not differ between the DAG and control oil intervention periods. Relative to control oil, DAG oil did not alter endpoint postprandial EE, fat oxidation, serum lipid profiles, or hepatic lipogenesis. However, DAG oil consumption reduced (P < 0.05) accumulation of body fat within trunk, android, and gynoid regions at the endpoint compared with control oil, although neither DAG nor control oil altered any of these variables during the 4-wk intervention period compared with their respective baseline levels. We conclude that although DAG oil is not effective in lowing serum lipids over a 4-wk intervention, it may be useful for reducing adiposity. [ABSTRACT FROM AUTHOR]

Fractional protein synthesis rates (FSR) are widely measured by the flooding dose technique via either an i.g. or an i.v. route. This study was conducted to compare differences in tracer incorporation and FSR in organs and tissues of fed piglets. The piglets were surgically implanted with catheters and randomly assigned to receive a flooding dose of Phe (1.5 mmol/kg body weight, 40 percent molar enrichment with [(2)H(5)]Phe) in saline administered via an i.p. or an i.v. route. [(2)H(5)]Phe free-pool enrichment in plasma increased logarithmically (P < 0.05) from 0 to 25% in the i.p. group, whereas it rose to a peak level within 3 min of the tracer injection and then decreased linearly (P < 0.05) in the i.v. group. Intracellular free-pool tracer enrichments in organs and tissues were within the range of the values measured for the plasma-free pool (25-27%), reaching the flooding status. Administration of the tracer via the i.p. and i.v. routes induced a logarithmical pattern (P < 0.05) of a surge in plasma cortisol concentrations within 30 min. Measurements of FSR in plasma, cardiac muscle, and skeletal muscles were lower (P < 0.05) in the i.p. than in the i.v. group due to the adverse effect of cortisol surge being more dramatic (P < 0.05) in the i.p. than in the i.v. group at 30 min of the post-tracer administration. We conclude that FSR may be measured by the flooding dose through an i.p. or an i.v. route and the i.p. route may underestimate FSR by the flooding dose for plasma, cardiac muscle, and skeletal muscles. This concern may be addressed by a fast regimen of sampling to be completed within 12-20 min after an i.p. route of tracer injection. [ABSTRACT FROM AUTHOR]

Fractional protein synthesis rates (FSR) are widely measured by the flooding dose technique via either an i.g. or an iv. route. This study was conducted to compare differences in tracer incorporation and FSR in organs and tissues of fed piglets. The piglets were surgically implanted with catheters and randomly assigned to receive a flooding dose of Phe 11.5 mmol/kg body weight, 40 percent molar enrichment with [2H5]Phe) in saline administered via an i.p. or an i.v. route. [2H5]Phe free-pool enrichment in plasma increased logarithmically (P < 0.05) from 0 to 25% in the i.p. group, whereas it rose to a peak level within 3 mm of the tracer injection and then decreased linearly (P < 0.05) in the iv. group. Intracellular free-pool tracer enrichments in organs and tissues were within the range of the values measured for the plasma-free pool (25-27%), reaching the flooding status. Administration of the tracer via the i.p. and iv. routes induced a logarithmical pattern (P < 0.05) of a surge in plasma cortisol concentrations within 30 mm. Measurements of FSR in plasma, cardiac muscle, and skeletal muscles were lower (P < 0.05) in the i.p. than in the i.v. group due to the adverse effect of cortisol surge being more dramatic (P < 0.05) in the i.p. than in the iv. group at 30 mm of the post-tracer administration. We conclude that FSR may be measured by the flooding dose through an i.p. or an i.v. route and the i.p. route may underestimate FSR by the flooding dose for plasma, cardiac muscle, and skeletal muscles. This concern may be addressed by a fast regimen of sampling to be completed within 12-20 mm after an i.p. route of tracer injection. [ABSTRACT FROM AUTHOR]