title: Plasma sterol evidence for decreased absorption and increased synthesis of cholesterol in insulin resistance and obesity.
abstract: BACKGROUND
  The rise in LDL with egg feeding in lean insulin-sensitive (LIS) participants is 2- and 3-fold greater than in lean insulin-resistant (LIR) and obese insulin-resistant (OIR) participants, respectively.
  
  
  OBJECTIVE
  We determined whether differences in cholesterol absorption, synthesis, or both could be responsible for these differences by measuring plasma sterols as indexes of cholesterol absorption and endogenous synthesis.
  
  
  METHODS
  Plasma sterols were measured by gas chromatography-mass spectrometry in a random subset of 34 LIS, 37 LIR, and 37 OIR participants defined by the insulin sensitivity index (S(I)) and by BMI criteria selected from a parent group of 197 participants. Cholestanol and plant sterols provide a measure of cholesterol absorption, and lathosterol provides a measure of cholesterol synthesis.
  
  
  RESULTS
  The mean (±SD) ratio of plasma total absorption biomarker sterols to cholesterol was 4.48 ± 1.74 in LIS, 3.25 ± 1.06 in LIR, and 2.82 ± 1.08 in OIR participants. After adjustment for age and sex, the relations of the absorption sterol-cholesterol ratios were as follows: LIS > OIR (P < 0.001), LIS > LIR (P < 0.001), and LIR > OIR (P = 0.11). Lathosterol-cholesterol ratios were 0.71 ± 0.32 in the LIS participants, 0.95 ± 0.47 in the LIR participants, and 1.29 ± 0.55 in the OIR participants. After adjustment for age and sex, the relations of lathosterol-cholesterol ratios were as follows: LIS < OIR (P < 0.001), LIS < LIR (P = 0.03), and LIR < OIR (P = 0.002). Total sterol concentrations were positively associated with S(I) and negatively associated with obesity, whereas lathosterol correlations were the opposite.
  
  
  CONCLUSIONS
  Cholesterol absorption was highest in the LIS participants, whereas cholesterol synthesis was highest in the LIR and OIR participants. Therapeutic diets for hyperlipidemia should emphasize low-cholesterol diets in LIS persons and weight loss to improve S(I) and to decrease cholesterol overproduction in LIR and OIR persons.
authors.affiliation: Division of Cardiology, University of Washington, Seattle, USA. nmbob@uw.edu
authors.forename: Pathmaja
authors.initials: P
authors.lastname: Paramsothy
authors.forename: Robert H
authors.initials: RH
authors.lastname: Knopp
authors.forename: Steven E
authors.initials: SE
authors.lastname: Kahn
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Retzlaff
authors.forename: Brian
authors.initials: B
authors.lastname: Fish
authors.forename: Lina
authors.initials: L
authors.lastname: Ma
authors.forename: Richard E
authors.initials: RE
authors.lastname: Ostlund
mesh_terms: D000042:Absorption; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood; D003430:Cross-Sectional Studies; D004032:Diet; D004311:Double-Blind Method; D004531:Eggs; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D007333:Insulin Resistance; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D010840:Phytosterols / Q000097:blood; D013261:Sterols / Q000097:blood*
chemical_list: D010840:Phytosterols; D013261:Sterols; C001521:lathosterol; D002784:Cholesterol