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

Metabolism. 2004 Feb;53(2):193-202. doi: 10.1016/j.metabol.2003.09.010.


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 (Vo(2)max), serum lipids, and post heparin (PH) plasma lipase activities were measured before and after 6 months of supervised exercise training. Difference in the response (Delta) 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 Delta). 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 Delta). 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 Delta). 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 Delta). Vo(2)max 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 Delta). 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anaerobic Threshold / physiology*
  • Apolipoproteins E / genetics*
  • Body Composition / physiology
  • Body Weight / physiology
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Diet
  • Energy Metabolism / physiology
  • Fatty Acids, Nonesterified / blood
  • Female
  • Humans
  • Lipase / metabolism
  • Lipids / blood*
  • Lipoprotein Lipase / blood
  • Lipoproteins / blood
  • Liver / enzymology
  • Male
  • Middle Aged
  • Oxygen Consumption / physiology*
  • Physical Fitness / physiology*


  • Apolipoproteins E
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Fatty Acids, Nonesterified
  • Lipids
  • Lipoproteins
  • Lipase
  • Lipoprotein Lipase