title: Phytosterols protect against diet-induced hypertriglyceridemia in Syrian golden hamsters.
abstract: BACKGROUND
  In addition to lowering LDL-C, emerging data suggests that phytosterols (PS) may reduce blood triglycerides (TG), however, the underlying mechanisms are not known.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  In 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).
  
  
  CONCLUSIONS
  Study 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.
authors.affiliation: Department of Exercise and Nutrition Sciences, University at Buffalo, Buffalo, NY 14214, USA. rideout@buffalo.edu.
authors.forename: Todd C
authors.initials: TC
authors.lastname: Rideout
authors.forename: Vanu
authors.initials: V
authors.lastname: Ramprasath
authors.forename: John D
authors.initials: JD
authors.lastname: Griffin
authors.forename: Richard W
authors.initials: RW
authors.lastname: Browne
authors.forename: Scott V
authors.initials: SV
authors.lastname: Harding
authors.forename: Peter J H
authors.initials: PJ
authors.lastname: Jones
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001384:Azetidines / Q000494:pharmacology / Q000627:therapeutic use; D008076:Cholesterol, HDL / Q000097:blood; D006224:Cricetinae; D059305:Diet, High-Fat / Q000009:adverse effects; D004353:Drug Evaluation, Preclinical; D000069438:Ezetimibe; D005227:Fatty Acids / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007408:Intestinal Absorption / Q000187:drug effects; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D050155:Lipogenesis; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D010840:Phytosterols / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D008076:Cholesterol, HDL; D005227:Fatty Acids; D010840:Phytosterols; D012333:RNA, Messenger; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D000069438:Ezetimibe