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.

Design: 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.

FIGURE 1.

A high-palmitate diet was associated with greater fat oxidation in men and women (n = 18). A: Mean (±SEM) effects of HPA and HOA diets on the RER in the fasted state (HPA: 0.855 ± 0.009; HOA: 0.870 ± 0.008) and fed state (HPA: 0.858 ± 0.008; HOA: 0.858 ± 0.006). B: Mean (±SEM) effects of diets on the rate of fatty acid oxidation expressed as a ratio to the REE at the end of an 11-h overnight fast or at the time of peak RER after an evening meal. *Diet effect, P= 0.04 (repeated-measures ANOVA specified for a crossover study, including sequence and treatment effects, with the baseline value as a covariate). FA OX, fatty acid oxidation; HOA, low palmitic acid and high oleic acid; HPA, high palmitic acid; REE, resting energy expenditure; RER, respiratory exchange ratio.

FIGURE 2.

Differential effects of HPA and HOA diets in men and women on serum lipid concentrations. A: Mean (±SEM) serum LDL-cholesterol concentration (n = 16) (HPA: 1.74 ± 0.13 mmol/L; HOA: 1.45 ± 0.13 mmol/L). B: Mean (±SEM) serum LDL:HDL ratio (n = 16) (HPA: 1.45 ± 0.16; HOA: 1.28 ± 0.17). Changes (HOA – HPA) in PCF1-Fasted score from the principal components analysis were directly correlated with changes in LDL (Spearman's rank r = 0.84, P < 0.001; n = 13) (C) and LDL:HDL (Spearman's rank r = 0.67, P = 0.012; n = 13) (D). *,**Diet effect (repeated-measures ANOVA specified for a crossover study, including sequence and treatment effects, with the baseline value as a covariate): *P < 0.05, **P < 0.01. HOA, low palmitic acid and high oleic acid; HPA, high palmitic acid; PCF1-Fasted, principal components analysis factor in the fasted state.

FIGURE 3.

A: Individual changes in the PA/OA ratio in serum PC during HPA and HOA diets (n = 18) (diet effect, P < 0.001; Wilcoxon's test). B: Individual changes in the PA/OA ratio in muscle PC (n = 16) (diet effect, P < 0.001; Wilcoxon's test). HOA, low palmitic acid and high oleic acid; HPA, high palmitic acid; PA/OA, palmitic acid/oleic acid; PC, phosphatidylcholine.

FIGURE 4.

Relative mean (±SEM) effects of HOA compared with HPA diets on genes that regulate fatty acid oxidation in skeletal muscle in the fed state. Genes: ACADM, acyl-CoA dehydrogenase, medium chain (also known as medium-chain acyl-CoA dehydrogenase or MCAD); HADH, hydroxyacyl-CoA dehydrogenase; INSIG-1, insulin induced gene 1 (women: 2.19 ± 0.72; men: 1.40 ± 0.16); PDK4, pyruvate dehydrogenase kinase 4; PGC-1α, peroxisome proliferation activator receptor coactivator−1α SCD1, stearoyl-CoA desaturase 1. *Diet effect (repeated-measures ANOVA specified for a crossover study, including sequence and treatment effects, with the baseline value as a covariate), P < 0.05. HOA, low palmitic acid and high oleic acid; HPA, high palmitic acid; REL., relative.