Abstract
BackgroundFatty acids have been shown to modulate intestinal cholesterol absorption in cells and animals, a process that is mediated by several transporter proteins. Of these proteins, Niemann-Pick C1-Like 1 (NPC1L1) is a major contributor to this process. The current study investigates the unknown mechanism by which fatty acids modulate cholesterol absorption.MethodsWe evaluated the effects of six fatty acids palmitic acid (PAM), oleic acid (OLA), linoleic acid (LNA), arachidonic acid (ARA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cholesterol uptake and transport in human enterocytes Caco-2 cells, and on the mRNA expression levels of NPC1L1, others proteins (ABCG5, ABCG8, ABCA1, ACAT2, MTP, Caveolin 1, Annexin-2) involved in cholesterol absorption, and SREBP-1 and SREBP-2 that are responsible for lipid metabolism.ResultsThe polyunsaturated fatty acids (PUFAs), especially for EPA and DHA, dose-dependently inhibited cholesterol uptake and transport in Caco-2 monolayer, while saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) had no inhibitory effects. EPA and DHA inhibited cholesterol absorption in Caco-2 monolayer might be caused by down-regulating NPC1L1 mRNA and protein levels, which were associated with inhibition of SREBP-1/− 2 mRNA expression levels.ConclusionResults from this study indicate that functional food containing high PUFAs may have potential therapeutic benefit to reduce cholesterol absorption. Further studies on this topic may provide approaches to control lipid metabolism and to promote health.
Highlights
Fatty acids have been shown to modulate intestinal cholesterol absorption in cells and animals, a process that is mediated by several transporter proteins
The results revealed that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at concentrations of 0.5 mmol/L and 1.0 mmol/L could significantly increased the mRNA levels of ATP-binding cassette sub-family G member 5 (ABCG5) (p < 0.05), whereas the other concentrations of fatty acids did not produce any significant effect
Our results showed that the cholesterol uptake and transport in Caco-2 cell monolayer was gradually inhibited with the increasing chain length and unsaturation of the fatty acids (Fig. 2 and Table 5), especially for arachidonic acid (ARA), EPA and DHA groups (p < 0.01)
Summary
Fatty acids have been shown to modulate intestinal cholesterol absorption in cells and animals, a process that is mediated by several transporter proteins. Of these proteins, Niemann-Pick C1-Like 1 (NPC1L1) is a major contributor to this process. An excessive intake of dietary cholesterol may lead to an increase in plasma cholesterol levels, lowdensity lipoprotein (LDL) cholesterol level, and atherosclerotic cardiovascular diseases (CVDs) risk [1]. Because the plasma cholesterol level is partly influenced by diets, the types of dietary fat may impact the cholesterol level and heart diseases. The primary prevention studies have shown the benefits of high-dose n-3 PUFAs supplements on metabolic risk factors; for instance, reductions in triacylglycerol levels have been reported [5, 15]
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