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  • br Discussion Of the age related


    Discussion Of the age-related differences in serum non-cholesterol sterols, we first deal with the cholesterol precursors. After birth, the markedly elevated serum desmosterol values decreased T7 Tag Peptide synthesis during the first year of life, and after 1 year of age they were similar between the other age groups. Since breast milk and infant formulas contain plenty of desmosterol, it T7 Tag Peptide synthesis is possible that the high serum desmosterol levels primarily reflected their increased dietary intake rather than cholesterol synthesis. Breast milk contains desmosterol about 1 mg/100 ml (0.03 mmol/l) depending on the state of lactation, so that at the age of 5 months its dietary intake can be up to 5–10 mg/d [13,[22], [23], [24]]. The concept that serum desmosterol is primarily diet-derived after birth is also supported by the finding that in this age group desmosterol did not correlate with any of the other cholesterol synthesis markers. On the other hand, the elevated squalene and cholestenol levels <1 year of age suggested that cholesterol synthesis was activated in this age group. Serum lathosterol level remained practically unchanged after birth throughout the childhood until it increased in adolescence. This finding resembles the results of an earlier study in 12-, 15-, and 18-year old boys, in whom serum lathosterol increased gradually after 12 years of age [14]. Accordingly, the present results suggest that during the first year of life, and from the age of 11 years, cholesterol synthesis is activated. However, during the first year of life, only the ‘early’ precursors squalene and cholestenol are elevated in serum, whereas in the adolescence serum lathosterol, the ‘late’ precursor is elevated. It remains open why the cholesterol synthesis pathway is differently activated in different ages. However, the lathosterol/desmosterol ratio showed that from 6 years of age cholesterol synthesis was practically similarly divided between the unsaturated Bloch and the saturated Kandutsch-Russel pathways. Plant sterols are not synthesized in the human body, and they are diet-derived. Breast milk contains very little plant sterols, about 0.1 mg/100 ml (0.003 mmol/l) [13], whereas infant formulas contain more, about 4 mg/100 ml (0.1 mmol/l) [24]. Thus, the low campesterol/cholestanol ratio, which reflects the plant sterol intake [21], suggested that the low serum plant sterol levels reflected primarily their low intake. Accordingly, in this age group they cannot be considered as cholesterol absorption markers. Serum cholesterol precursors, plant sterols, and cholestanol are biomarkers of whole-body cholesterol synthesis and absorption efficiency validated in several adult populations [[15], [16], [17], [18], [19]]. To be certain that they operated as expected also in this child population, we interrelated the cholesterol precursors with each other in every age group as well as the absorption markers. In addition, cholesterol homeostasis was checked by relating the precursor sterols to the absorption markers in every age group. It seems evident that cholestenol and lathosterol were the most reliable biomarkers of cholesterol synthesis in every age group. Interestingly, only in the age group 6–10 years, squalene correlated with all other precursors. Serum squalene was originally reported as a marker of cholesterol synthesis especially in non-steady-state situations [25], but later on, it was not associated with cholesterol synthesis except in subjects with type 2 diabetes [19]. Its correlation with the other precursors, especially in the age group 6–10 yrs, probably reflects a burst in cholesterol synthesis during these years. Serum plant sterols except stigmasterol were tightly interrelated. In the age group <1 year, they did not correlate with cholestanol, but from the age of 1 year, plant sterols and cholestanol were interrelated. Stigmasterol behaved differently, it associated only weakly with the other plant sterols and cholestanol in the whole study population. Stigmasterol was neither associated with any of the cholesterol precursors. Accordingly, even though being a plant sterol, stigmasterol cannot be considered as a marker of cholesterol absorption. Stigmasterol is the only plant sterol which in large concentrations, simulating human phytosterolemia, is able to interfere with cholesterol homeostasis. Thus, in adrenal cells of mice lacking ABCG5 and ABCG8 receptors, it reduced cholesterol synthesis by inhibiting SREBP-2 processing, and it was able to activate the liver X receptor [26].