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HepG2 cells were incubated with a 16.5:1.7:1 ratio of cholesterol:sitosterol:campesterol (CSC), a ratio of the major sterols observed in the plasma of phytosterolemia patients, or with cholesterol alone in combination with [14C]acetate for 24 h and the radioactivity incorporated into lipids determined. Cells incubated with CSC exhibited a 40% reduction in cholesterol esterification (p < 0.05) compared to cells incubated with cholesterol alone. In addition, a 17.5‐fold reduction (p < 0.05) in total cholesterol (cholesterol plus cholesteryl ester) synthesis from [14C]acetate was observed in cells incubated with CSC compared to cholesterol alone. Low‐density lipoprotein receptor (LDLR) mRNA abundance was lower in cells incubated with CSC compared to cells incubated with cholesterol alone. Our results suggest that incubation of HepG2 cells with a ratio of sterols that mimic the plasma concentration seen in phytosterolemia patients reduces cholesterol esterification, total cholesterol synthesis, and inhibits LDLR mRNA abundance. We suggest that future cell and animal‐based work on phytostosterolemia might employ this methodology to serve as a novel paradigm of the disease. [ABSTRACT FROM AUTHOR]

Abstract: Although phytosterols, plant‐derived sterol‐like components, are well known for their cholesterol‐lowering properties, their atherogenic potential is still under debate. Although they are known to share structural similarities with cholesterol, it is unclear whether their oxidized forms (oxyphytosterols) have the capacity to mediate proinflammatory responses in macrophages. In the present study, bone marrow‐derived macrophages were treated with oxidized low‐density lipoproteins, oxyphytosterols (7keto‐sito/campesterol [7keto‐sit/camp] or 7‐beta‐hydroxy‐sito/campesterol [7βOH‐sit/camp]), nonoxidized phytosterol (β‐sitosterol), or carrier‐control (cyclodextrin) in a dose‐ and time‐dependent manner. Inflammatory cytokine release, activity, and the corresponding mRNA expression levels were analyzed. 7βOH‐sit/camp, rather than 7keto‐sit/camp, induced a modest proinflammatory response in wild‐type cells derived from C57Bl/6 mice. The observed mild inflammatory effects are independent of the low‐density lipoprotein receptor and Cluster of differentiation 36/Scavenger receptor‐a. These data suggest that exogenously added oxyphytosterols do not affect macrophage‐mediated inflammatory responses, at least in vitro. [ABSTRACT FROM AUTHOR]

Phytosterols are recognized as functional food components with cholesterol reducing properties in humans. The formation of phytosterol oligomers as a result of the thermo-oxidative degradation of sitosterol is shown to occur. The existence of oligomers is demonstrated by size exclusion chromatography (SEC) and confirmed by combined SEC-atmospheric pressure chemical ionization mass spectrometry (SEC/APCI-MS). A speculative structure for the sitosterol dimer with 3,7′ linkage is proposed consistent with data from tandem mass spectrometry and exact mass measurements. Higher molecular weight species arising from the formation of trimers or higher oligomers are seen in the mass spectra. Fragments of sitosterol formed by thermo-oxidative processes are also shown to oligomerize and their common structural characteristics are demonstrated by tandem mass spectrometry. The results presented provide evidence for the possible formation of oligomeric species involving sterols in addition to those known for acylglycerides in vegetable oils subjected to extreme oxidative stress such as in frying. [ABSTRACT FROM AUTHOR]

Phytosterols occur in high concentration in canola ( Brassica napus L.) and other vegetable oils such as from the borage plant Echium ( Echium plantagineum L.). We investigated if Atlantic salmon ( Salmo salar) digest and accumulate dietary phytosterols in significant amounts in muscle and liver. Phytosterols are lipid soluble, lower cholesterol and reduce the risk of coronary heart disease in humans. We aimed to determine if fatty fish, such as salmon, can be used as a delivery source of this functional food component. Three diets containing canola oil (CO), Echium oil (EO) and fish oil (FO) were fed to Atlantic salmon smolt over 9 weeks. The digestibility of natural abundances of phytosterols by Atlantic salmon was poor compared to cholesterol. However, phytosterols accumulated in liver and muscle of fish. Significantly increased concentrations of 24-methylenecholesterol, campesterol, β-sitosterol and total phytosterol occurred in livers of EO fed fish compared to FO fed fish. Campesterol concentrations increased in CO fed fish compared to the FO fed fish. We demonstrated that natural abundances of dietary phytosterols are digested by and accumulated in liver and white muscle of Atlantic salmon smolt. However, phytosterol levels in salmon muscle will not be a major source of phytosterols in human diets and would not be expected to significantly effect human cardiovascular health. [ABSTRACT FROM AUTHOR]

ATP binding cassette transporter G5 (ABCG5) and ATP binding cassette transporter G8 (ABCG8) have been suggested to transport absorbed plant sterols and cholesterol from enterocytes to the intestinal lumen and from hepatocytes to bile. It has been thought that mutations of ABCG5 or ABCG8 cause the deposition of plant sterols in the body. In the present study, lymphatic absorption of various plant sterols and their deposition in various tissues was investigated in stroke-prone spontaneously hypertensive rats (SHRSP), having a mutation in Abcg5 and depositing plant sterols in the body. The order of lymphatic 24-h recovery of plant sterols was as follows: campesterol > sitosterol > brassicasterol > stigmasterol = sitostanol. When SHRSP were fed a diet containing one of the plant sterols, the depositions of campesterol and sitosterol were comparatively higher than those of brassicasterol, stigmasterol and sitostanol. Highly positive correlations were obtained between lymphatic recovery of plant sterols and their levels in plasma, liver, adipose tissue and heart. The tendency of differential absorption of plant sterols to the lymph in SHRSP was similar to that in normal Wistar rats previously reported by us (Hamada et al. Lipids 41:551–556, 2006). These observations suggest that differential absorption of various plant sterols is kept in SHRSP in spite of a mutation in Abcg5. [ABSTRACT FROM AUTHOR]