title: Dietary intake of palmitate and oleate has broad impact on systemic and tissue lipid profiles in humans.
abstract: BACKGROUND
  Epidemiologic evidence has suggested that diets with a high ratio of palmitic acid (PA) to oleic acid (OA) increase risk of cardiovascular disease (CVD).
  
  
  OBJECTIVE
  To gain additional insights into the relative effect of dietary fatty acids and their metabolism on CVD risk, we sought to identify a metabolomic signature that tracks with diet-induced changes in blood lipid concentrations and whole-body fat oxidation.
  
  
  METHODS
  We applied comprehensive metabolomic profiling tools to biological specimens collected from 18 healthy adults enrolled in a crossover trial that compared a 3-wk high-palmitic acid (HPA) with a low-palmitic acid and high-oleic acid (HOA) diet.
  
  
  RESULTS
  A principal components analysis of the data set including 329 variables measured in 15 subjects in the fasted state identified one factor, the principal components analysis factor in the fasted state (PCF1-Fasted), which was heavily weighted by the PA:OA ratio of serum and muscle lipids, that was affected by diet (P < 0.0001; HPA greater than HOA). One other factor, the additional principal components analysis factor in the fasted state (PCF2-Fasted), reflected a wide range of acylcarnitines and was affected by diet in women only (P = 0.0198; HPA greater than HOA). HOA lowered the ratio of serum low-density lipoprotein to high-density lipoprotein (LDL:HDL) in men and women, and adjustment for the PCF1-Fasted abolished the effect. In women only, adjustment for the PCF2-Fasted eliminated the HOA-diet effect on serum total- and LDL-cholesterol concentrations. The respiratory exchange ratio in the fasted state was lower with the HPA diet (P = 0.04), and the diet effect was eliminated after adjustment for the PCF1-Fasted. The messenger RNA expression of the cholesterol regulatory gene insulin-induced gene-1 was higher with the HOA diet (P = 0.008).
  
  
  CONCLUSIONS
  These results suggest that replacing dietary PA with OA reduces the blood LDL concentration and whole-body fat oxidation by modifying the saturation index of circulating and tissue lipids. In women, these effects are also associated with a higher production and accumulation of acylcarnitines, possibly reflecting a shift in fat catabolism.
authors.affiliation: Departments of Pediatrics (CLK), Medicine (CLK and KC), and Medical Biostatistics (JYB), University of Vermont, Burlington, VT, and the Stedman Nutrition and Metabolism Center (RS, JB, OI, TRK, and DMM) and Departments of Medicine (TRK and DMM) and Pharmacology and Cancer Biology (DMM), Duke University, Durham, NC.
authors.forename: C Lawrence
authors.initials: CL
authors.lastname: Kien
authors.forename: Janice Y
authors.initials: JY
authors.lastname: Bunn
authors.forename: Robert
authors.initials: R
authors.lastname: Stevens
authors.forename: James
authors.initials: J
authors.lastname: Bain
authors.forename: Olga
authors.initials: O
authors.lastname: Ikayeva
authors.forename: Karen
authors.initials: K
authors.lastname: Crain
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Koves
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Muoio
mesh_terms: D000293:Adolescent; D000328:Adult; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism; D015331:Cohort Studies; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood*; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D055432:Metabolomics / Q000379:methods; D018482:Muscle, Skeletal / Q000378:metabolism*; D019301:Oleic Acid / Q000009:adverse effects* / Q000627:therapeutic use; D019308:Palmitic Acid / Q000009:adverse effects*; D012307:Risk Factors; D012727:Sex Characteristics; D015854:Up-Regulation; D014707:Vermont / Q000453:epidemiology; D055815:Young Adult
chemical_list: D004041:Dietary Fats; C108626:INSIG1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids; D008565:Membrane Proteins; C116917:acylcarnitine; D019301:Oleic Acid; D019308:Palmitic Acid; D002331:Carnitine