Reversal of small, dense LDL subclass phenotype by weight loss is associated with impaired fat oxidation

Abstract

Adiposity is more prevalent among individuals with a predominance of small, dense low-density lipoprotein (LDL) (pattern B) particles than among those with larger LDL (pattern A). We tested for differences in resting energy expenditure (REE) and respiratory quotient (RQ) in overweight men with pattern A (n = 36) or pattern B (n = 60). Men consumed a standardized isoenergetic diet for 3 weeks after which a ~9 kg weight loss was induced by caloric deficit for 9 weeks, followed by 4 weeks of weight stabilization. REE and RQ were measured by indirect calorimetry before and after weight loss. Results were analyzed separately in pattern B men who converted to pattern A (B→A; n = 35) and those who did not (B→B; n = 25). At baseline, B→B men had higher trunk fat, triacylglycerol (TG) and insulin concentrations, homeostasis model assessment of insulin resistance (HOMA(IR)), and smaller LDL particles compared to B→A men and baseline pattern A men who remained pattern A (A→A; n = 35). REE normalized to fat-free mass did not change after weight loss. RQ decreased in A→A men, increased in B→A men, and did not change significantly in B→B men after weight loss. Calculated fat oxidation rates paralleled the RQ results. Baseline plasma TG concentrations were positively correlated with RQ and inversely correlated with the magnitude of weight loss achieved for a given prescribed energy reduction in the entire study population. Pattern B men who converted to pattern A with weight loss may have an underlying impairment in fat oxidation that predisposes to both dyslipidemia and an impaired ability to achieve weight loss by energy restriction.

Figure 1

Pre- and post-weight loss body mass indices are plotted in relation to LDL diameter for pattern A (n=36; open square) and pattern B men (n=60; closed circle). Where 257.5 angstroms defines the threshold above which LDL subclass pattern is defined as pattern B and below which LDL subclass pattern is defined as pattern A (horizontal dotted line), a BMI of 25 was the pre-specified study goal (vertical dotted line) in this weight loss intervention (1). A higher percentage of pattern A compared to pattern B men was able to meet the study goal.

Figure 2

RQ measurements before (open circle) and after (closed circle) weight loss as a function of conversion phenotype (A→A, B→A or B→B). RQ was decreased after weight loss in A→A men and increased in B→A men as determined by analysis of variance and post-hoc Tukey's tests (p=0.007). The change in the B→B group was not significantly different from the two other groups.

Figure 3

Linear regression analysis of baseline triglyceride and baseline respiratory quotient in men enrolled in weight loss intervention (n=95; r²=0.05; p=0.02).

Figure 4

Figure 4a: Linear regression analysis of baseline triglyceride and weight loss per calorie reduction in men undergoing weight loss (n=95; r²= 0.07; p=0.01). Figure 4b: Linear regression analysis of baseline RQ and weight loss per calorie reduction in weight loss group (n=95) at baseline (r²= 0.035; p=0.069).