Abstract
BackgroundIn addition to lowering LDL-C, emerging data suggests that phytosterols (PS) may reduce blood triglycerides (TG), however, the underlying mechanisms are not known.MethodsWe examined the TG-lowering mechanisms of dietary PS in Syrian golden hamsters randomly assigned to a high fat (HF) diet or the HF diet supplemented with PS (2%) for 6 weeks (n = 12/group). An additional subset of animals (n = 12) was provided the HF diet supplemented with ezetimibe (EZ, 0.002%) as a positive control as it is a cholesterol-lowering agent with known TG-lowering properties.ResultsIn confirmation of diet formulation and compound delivery, both the PS and EZ treatments lowered (p < 0.05) intestinal cholesterol absorption (24 and 31%, respectively), blood non-HDL cholesterol (61 and 66%, respectively), and hepatic cholesterol (45 and 55%, respectively) compared with the HF-fed animals. Blood TG concentrations were lower (p < 0.05) in the PS (49%) and EZ (68%)-treated animals compared with the HF group. The TG-lowering response in the PS-supplemented group was associated with reduced (p < 0.05) intestinal SREBP1c mRNA (0.45 fold of HF), hepatic PPARα mRNA (0.73 fold of HF), hepatic FAS protein abundance (0.68 fold of HD), and de novo lipogenesis (44%) compared with the HF group. Similarly, lipogenesis was lower in the EZ-treated animals, albeit through a reduction in the hepatic protein abundance of ACC (0.47 fold of HF).ConclusionsStudy results suggest that dietary PS are protective against diet-induced hypertriglyceridemia, likely through multiple mechanisms that involve modulation of intestinal fatty acid metabolism and a reduction in hepatic lipogenesis.
Highlights
In addition to lowering LDL-C, emerging data suggests that phytosterols (PS) may reduce blood triglycerides (TG), the underlying mechanisms are not known
LDL-C levels have decreased among US adults in recent years largely due to the widespread and effective use of lipid lowering medication, hypertriglyceridemia is increasingly prevalent with 33.1% of Americans having borderline high triglyceride (TG) levels [1]
Previous work suggests that PS may be effective in reducing TG in subjects with established, overt hypertriglyceridemia, it is unknown if PS provides protection against diet-induced increases in TG following high fat feeding
Summary
In addition to lowering LDL-C, emerging data suggests that phytosterols (PS) may reduce blood triglycerides (TG), the underlying mechanisms are not known. LDL-C levels have decreased among US adults in recent years largely due to the widespread and effective use of lipid lowering medication, hypertriglyceridemia is increasingly prevalent with 33.1% of Americans having borderline high triglyceride (TG) levels [1] This mean increase in TG concentrations amongst men and women over the past 20 years has coincided with the alarming obesity trend and is further associated with increased risk of acute pancreatitis and cardiovascular disease (CVD) [2]. The precise mechanism (s) responsible for the TG-lowering effects of PS are not known, we recently observed an increase in fecal saturated fatty acid excretion in C57Bl6 mice fed a PSenriched diet, suggesting a possible interference with intestinal fat absorption [7]. We utilized EZ as a comparative control as it is another well-characterized cholesterol-absorptive inhibitor that is recognized to reduce circulating TG concentrations in humans and a previous study using the Syrian golden hamster [8]
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