Apolipoprotein e genotype and changes in serum lipids and maximal oxygen uptake with exercise training

Physical activity improves lipid levels by altering triglyceride (TG) metabolism. Apolipoprotein E (Apo E) facilitates TG clearance by mediating lipoprotein binding to hepatic receptors, but Apo E also has less defined roles in skeletal muscle and nervous tissue. This study examined if variants in Apo E genotype affect the lipid and physiologic response to exercise training. Seven centers genetically screened 566 individuals to recruit 120 subjects into 6 gender-specific cohorts equal for the most common Apo E genotypes: E2/3, E3/3, and E3/4. Anthropometics, exercise capacity (V o 2max), serum lipids, and post heparin (PH) plasma lipase activities were measured before and after 6 months of supervised exercise training. Difference in the response (Δ) to training among the Apo E genotypes was the primary outcome variable. Differences in pretraining serum lipids among the Apo E genotypes mimicked those observed in population studies: TGs were slightly higher in E2/3 subjects, whereas low-density lipoprotein (LDL)-cholesterol (C) was lower ( P = not significant [NS] ). TGs decreased 11% with training for the entire cohort ( P < .0001) and 7%, 12%, and 14% for the Apo E 2/3, 3/3 and 3/4 groups, respectively ( P = NS for Δ). LDL-C did not change in the entire cohort, but decreased slightly in the 2/3 and 3/3 subjects and increased 4% in the 3/4 group ( P = NS for Δ). High-density lipoprotein (HDL)-C increased 2% for the entire cohort ( P = .06) due to a 6% increase in the 3/3 group ( P = .07 for Δ). Total cholesterol (TC)/HDL and LDL/HDL decreased with training in the 2/3 and 3/3 groups, but increased in the 3/4 subjects and these responses differed among the genotypes ( P < .05 for Δ). V o 2max increased 9% to 10% for the entire cohort, but only 5% in the 3/3 subjects versus 13% in the 2/3 and 3/4 groups and these differences were significantly different among the genotypes ( P < .01 for Δ). This is the first prospective study to demonstrate that the serum lipid response to exercise training differs by Apo E genotype in a pattern consistent with known metabolic differences among the variants. Surprisingly, Apo E genotype also affected the increase in aerobic capacity produced by exercise training possibly via undefined effects on nerve and skeletal muscle function.