title: Effects of a 2-y dietary weight-loss intervention on cholesterol metabolism in moderately obese men.
abstract: BACKGROUND
  Long-term dietary weight loss results in complex metabolic changes. However, its effect on cholesterol metabolism in obese subjects is still unclear.
  
  
  OBJECTIVE
  We assessed the effects of 2 y of weight loss achieved with various diet regimens on phytosterols (markers of intestinal cholesterol absorption), lanosterol (marker of de novo cholesterol synthesis), and changes in apolipoprotein concentrations.
  
  
  METHODS
  We conducted the 2-y Dietary Intervention Randomized Controlled Trial (DIRECT-a study of low-fat, Mediterranean, and low-carbohydrate diets). We assessed circulating phytosterol and lanosterol concentrations and their ratios to cholesterol and apolipoproteins A-I and B-100 in 90 DIRECT participants at 0, 6, and 24 mo.
  
  
  RESULTS
  We observed a significant upregulation of the markers of cholesterol absorption (campesterol: +16.8%, P < 0.001) and a downregulation of the markers of cholesterol synthesis (lanosterol: -16.5%, P = 0.008) during the active weight-loss phase (first 6 mo, weight loss of 5%, 6%, and 10% in the 3 diet groups, respectively), followed by a rebound (campesterol: -6.2%, P = 0.045; lanosterol: +43.7%, P < 0.001) during the next 18 mo (weight gain of 1%, 1%, and 2% in the 3 diet groups, respectively). HDL cholesterol continuously increased during the study (17.0%, P < 0.001), whereas LDL cholesterol remained constant. At the end of the 24-mo follow-up period, campesterol (P < 0.001) and lanosterol (P = 0.016) amounts were significantly higher than baseline values. The concentration of apolipoprotein B-100 correlated with cholesterol metabolism (ρ = 0.299 and P = 0.020 for lanosterol; ρ = -0.105 and NS for campesterol), and the homeostasis model assessment of insulin resistance correlated with lanosterol (ρ = 0.09, P = 0.001).
  
  
  CONCLUSIONS
  Long-term weight loss is related to a characteristic response suggestive of altered cholesterol and apolipoprotein metabolism. Various diets have a similar effect on these effects. DIRECT is registered at clinicaltrials.gov as NCT00160108.
authors.affiliation: University Institute of Clinical Chemistry, Inselspital - Bern University Hospital, Switzerland. alexander.leichtle@insel.ch
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Leichtle
authors.forename: Christin
authors.initials: C
authors.lastname: Helmschrodt
authors.forename: Uta
authors.initials: U
authors.lastname: Ceglarek
authors.forename: Iris
authors.initials: I
authors.lastname: Shai
authors.forename: Yaakov
authors.initials: Y
authors.lastname: Henkin
authors.forename: Dan
authors.initials: D
authors.lastname: Schwarzfuchs
authors.forename: Rachel
authors.initials: R
authors.lastname: Golan
authors.forename: Yftach
authors.initials: Y
authors.lastname: Gepner
authors.forename: Meir J
authors.initials: MJ
authors.lastname: Stampfer
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.forename: Joachim
authors.initials: J
authors.lastname: Thiery
authors.forename: Georg M
authors.initials: GM
authors.lastname: Fiedler
mesh_terms: D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood; D053299:Apolipoprotein B-100 / Q000097:blood; D001835:Body Weight / Q000502:physiology; D002784:Cholesterol / Q000378:metabolism*; D004038:Diet, Reducing / Q000379:methods* / Q000592:standards; D006801:Humans; D007810:Lanosterol / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000178:diet therapy* / Q000378:metabolism*; D010840:Phytosterols / Q000097:blood; D018709:Statistics, Nonparametric; D015431:Weight Loss / Q000502:physiology*
chemical_list: D016632:Apolipoprotein A-I; D053299:Apolipoprotein B-100; D010840:Phytosterols; D007810:Lanosterol; D002784:Cholesterol