Abstract
The prevalence of metabolic disorders characterized by chronic inflammation has been on a sharp rise for decades. As such, tools that address metabolic and inflammatory dysregulation are of great importance. Plant stanols are well-known for reducing intestinal cholesterol absorption and may also have direct anti-inflammatory effects. In this study, our aim was to investigate to what extent the benefits of dietary plant stanol supplementation depend on dietary cholesterol intake in an experimental mouse model for cholesterol-induced metabolic inflammation. Here, we used Ldlr−/− mice transplanted with Npc1nih-derived bone marrow, featuring feature bone marrow-derived immune cells characterized by chronic inflammation induced by lysosomal lipid accumulation. Npc1nih- and Npc1wt-transplanted mice were placed on either a high fat, high cholesterol (HFC) or on a chow diet low in cholesterol, with or without 2% plant stanols supplementation. At the end of the study, the metabolic and inflammatory status of the mice was analyzed. Plant stanol supplementation to the HFC diet reduced liver cholesterol levels and improved lipid metabolism and liver inflammation, particularly in Npc1nih-tp mice. In contrast, plant stanol supplementation to the chow diet did not significantly improve the aforementioned parameters, though similar reductive trends to those in the HFC diet setting were observed regarding liver cholesterol accumulation and liver inflammatory markers. The effects of dietary plant stanol supplementation on dietary cholesterol-induced inflammation are largely dependent on dietary cholesterol intake. Future research should verify whether other models of metabolic inflammation exhibit similar stanol-related effects on inflammation.
Highlights
Despite efforts to raise awareness on the importance of a healthy lifestyle, the prevalence of obesity accompanied by metabolic syndrome has been on a sharp rise for decades [1].Individuals who meet at least three of the following criteria are diagnosed with metabolic syndrome: increased hip-to-waist ratio, hypertriglyceridemia, hyperglycemia, low highdensity lipoprotein plasma levels, and hypertension
To determine to what extent the effects of plant stanols on lipid metabolism are dependent on diet, we analyzed plasma and liver cholesterol levels of Npc1wt -tp mice and of Npc1nih -tp mice placed on an HFC or chow diet for 15 weeks
As expected, adding plant stanols to the HFC diet effectively reduced plasma and hepatic cholesterol levels in both experimental groups (Figure 2), whereas plant stanol supplementation of the chow diet had no significant effect on plasma and liver cholesterol levels in either experimental group (Figure 2)
Summary
Despite efforts to raise awareness on the importance of a healthy lifestyle, the prevalence of obesity accompanied by metabolic syndrome has been on a sharp rise for decades [1].Individuals who meet at least three of the following criteria are diagnosed with metabolic syndrome: increased hip-to-waist ratio, hypertriglyceridemia, hyperglycemia, low highdensity lipoprotein plasma levels, and hypertension. It is clear that a concerted effort is required to increase the awareness of the strengths of lifestyle-related prevention strategies as well as to develop efficient strategies to target metabolic syndrome and its associated disease burden. Studies suggest that plant stanols have immunomodulatory and anti-inflammatory effects [4,5], and it has been suggested that these effects might occur independently from their ability to reduce cholesterol absorption [4]. This assumption of independency has yet to be validated in in vivo models for metabolic diseases. Our group showed that dietary plant stanol supplementation reduces hepatic cholesterol levels, ameliorates liver inflammation, and shifts blood immune cells towards a less pro-inflammatory profile in a murine model of Niemann–Pick type C1
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