In vitro effects of sitosterol and sitostanol on mitochondrial respiration in human brown adipocytes, myotubes and hepatocytes

Emmani B M Nascimento,Maurice Konings,Wouter D Van Marken Lichtenbelt,Patrick Schrauwen,Albert K Groen,Gert Schaart,Dieter Lütjohann,Jogchum Plat

doi:10.1007/s00394-019-02052-y

Abstract

PurposeLowering of LDL cholesterol levels by plant sterols and stanols is associated with decreased risk of cardiovascular disease in humans. Plant sterols and stanols also lower triacylglycerol (TG). However, it is not fully understood how reduction in TG is achieved and what the full potential of plant sterols and stanols is on whole-body metabolism. We here hypothesize that high levels of plant sterols and stanols stimulate whole-body energy expenditure, which can be attributed to changes in mitochondrial function of brown adipose tissue (BAT), skeletal muscle and liver.MethodsPhytosterolemic mice were fed chow diets for 32 weeks to examine whole-body weight gain. In vitro, 24-h incubation were performed in adipocytes derived from human BAT, human myotubes or HepG2 human hepatocytes using sitosterol or sitostanol. Following mitochondrial function was assessed using seahorse bioanalyzer.ResultsChow feeding in phytosterolemic mice resulted in diminished increase in body weight compared to control mice. In vitro, sitosterol or sitostanol did not change mitochondrial function in adipocytes derived from human BAT or in cultured human myotubes. Interestingly, maximal mitochondrial function in HepG2 human hepatocytes was decreased following sitosterol or sitostanol incubation, however, only when mitochondrial function was assessed in low glucose-containing medium.ConclusionsBeneficial in vivo effects of plant sterols and stanols on lipid and lipoprotein metabolism are well recognized. Our results indicate that alterations in human mitochondrial function are apparently not involved to explain these beneficial effects.

Highlights

Dietary plant sterols or stanols lower intestinal cholesterol absorption, which results in lower serum LDL cholesterol
We examined the effects of long-term (24 h) incubation of sitosterol or sitostanol on cultured adipocytes derived from human brown adipose tissue (BAT) or white adipose tissue (WAT)
To complete our series of experiments, we examined whether skeletal muscle mitochondrial function was altered, because human subjects with the metabolic syndrome benefitted from sitosterol or sitostanol-mediated TG reductions

Summary

Introduction

Dietary plant sterols or stanols lower intestinal cholesterol absorption, which results in lower serum LDL cholesterol. A daily intake of 2-g plant sterols and/or plant stanols lowers serum LDL cholesterol up to 10% [1]. LDL cholesterol is a causal risk factor for the development of cardiovascular disease, lowering serum LDL cholesterol would reduce the risk to develop cardiovascular disease. Besides lowering serum LDL cholesterol, plant sterols and plant stanols lower serum triacylglycerol (TG) levels, especially in subjects with elevated serum TG who are at risk to develop metabolic disease [2]. The evidence that fasting TGs are independent risk factors for cardiovascular disease is weak [3], accumulating evidence suggests that postprandial TGs are independent risk factors [4, 5]. Several studies have demonstrated TG-lowering effects of plant sterols and stanols [6,

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