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, thus 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].
Although 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]. So far, several studies have demonstrated TG-lowering effects of plant sterols and stanols [
6,
7],however, the mechanism behind the TG-lowering effects of plants sterols and stanols remains unclear. In C57Bl/6 mice on a high-fat diet (HFD), both plant sterols and stanols lowered hepatic VLDL production [
8], however, the molecular explanation for this effect remains so far unknown. Furthermore, we have demonstrated in humans that plant stanol consumption strongly reduced serum concentration of large TG-rich VLDL in subjects with the metabolic syndrome [
9]. Besides reduced hepatic VLDL-1 production, the reduced concentration of VLDL-1 particles could also be explained through enhanced TG clearance from the circulation. Previously, we indirectly excluded a role for LPL-mediated TG uptake in white adipose tissue (WAT) and muscle. No change was observed in circulating concentrations of apoC2 and apoC3 during the postprandial phase, the activator, and inhibitor of LPL, respectively [
10]. However, recent evidence suggests that—at least in mice—a considerable fraction of circulating TGs is cleared from the circulation by brown adipose tissue (BAT). BAT, as opposed to white adipose tissue (WAT), is able to combust lipids and glucose as fuel resulting in heat production [
11]. Uncoupling protein 1 (UCP1) present in the mitochondria of brown adipocytes, uncouples the proton gradient in the electron transport chain generating heat instead of ATP. Because of this hallmark, BAT has been coined an important target to combat metabolic disease [
12,
13]. With respect to lipid metabolism, BAT stimulation via cold exposure in humans specifically showed uptake of the FFA tracer
18F-FTHA which was not observed in WAT or muscle [
14]. Cold-exposed mice subjected to an oral lipid tolerance test, did not show changes in TG concentrations due to active BAT [
15]. Also pharmacological intervention with metformin in mice, lowered circulating levels of TGs via increased VLDL-TG clearance by BAT [
16]. Activated BAT might be an important player in lipid metabolism,however, it remains unexplored whether BAT plays a role in the action of plant sterols and stanols. Also the involvement of other organs with high mitochondrial density should not be overlooked. Therefore, we here examined how increasing plant sterols and stanols in mice affected whole-body metabolism in mice. Furthermore, we investigated if the TG-lowering action of plant sterols and plant stanols could be attributed to mitochondrial activity in BAT, skeletal muscle or liver.