Abstract
Non-cholesterol sterols are validated biomarkers for intestinal cholesterol absorption and endogenous cholesterol synthesis. However, their use in metabolic disturbances has not been systematically explored. Therefore, we conducted a systematic review to provide an overview of non-cholesterol sterols as markers for cholesterol metabolism in different metabolic disorders. Potentially relevant studies were retrieved by a systematic search of three databases in July 2018 and ninety-four human studies were included. Cholesterol-standardized levels of campesterol, sitosterol and cholestanol were collected to reflect cholesterol absorption and those of lathosterol and desmosterol to reflect cholesterol synthesis. Their use as biomarkers was examined in the following metabolic disorders: overweight/obesity (n = 16), diabetes mellitus (n = 15), metabolic syndrome (n = 5), hyperlipidemia (n = 11), cardiovascular disease (n = 17), and diseases related to intestine (n = 16), liver (n = 22) or kidney (n = 2). In general, markers for cholesterol absorption and synthesis displayed reciprocal patterns, showing that cholesterol metabolism is tightly regulated by the interplay of intestinal absorption and endogenous synthesis. Distinctive patterns for cholesterol absorption or cholesterol synthesis could be identified, suggesting that metabolic disorders can be classified as ‘cholesterol absorbers or cholesterol synthesizers’. Future studies should be performed to confirm or refute these findings and to examine whether this information can be used for targeted (dietary) interventions.
Highlights
Cholesterol metabolism is tightly regulated, since cholesterol plays an essential role in many physiological processes [1]
In the vast majority of studies, total cholesterol (TC)-standardized levels of campesterol, sitosterol and cholestanol on the one hand, and TC-standardized levels of lathosterol and desmosterol on the other hand, showed comparable patterns. This underlines their use as biomarkers for cholesterol absorption and cholesterol synthesis, respectively
Non-cholesterol biomarkers displayed reciprocal patterns, indicating that cholesterol metabolism is tightly regulated by the balance of intestinal absorption and endogenous synthesis
Summary
Cholesterol metabolism is tightly regulated, since cholesterol plays an essential role in many physiological processes [1]. Cells have different possibilities to regulate cellular free cholesterol concentrations such as changing low-density lipoprotein-receptor expression, endogenous synthesis, intracellular esterification and excretion [2]. Cholesterol can be obtained from de novo endogenous cholesterol synthesis, which occurs virtually in every single cell [3], and from intestinal absorption of dietary and biliary cholesterol. An inverse relationship exists between cholesterol absorption and synthesis, whereby low intestinal cholesterol absorption is compensated by upregulation of cholesterol synthesis and vice versa [4]. To study the processes of intestinal cholesterol absorption and endogenous cholesterol synthesis in humans, several approaches can be used. Intestinal cholesterol absorption can be measured by using radioisotope tracer or stable isotope tracer methods
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