title: Apolipoprotein E genotype and changes in serum lipids and maximal oxygen uptake with exercise training.
abstract: 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.
authors.affiliation: Hartford Hospital, Hartford, CT, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Thompson
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Tsongalis
authors.forename: Richard L
authors.initials: RL
authors.lastname: Seip
authors.forename: Cherie
authors.initials: C
authors.lastname: Bilbie
authors.forename: Mary
authors.initials: M
authors.lastname: Miles
authors.forename: Robert
authors.initials: R
authors.lastname: Zoeller
authors.forename: Paul
authors.initials: P
authors.lastname: Visich
authors.forename: Paul
authors.initials: P
authors.lastname: Gordon
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Angelopoulos
authors.forename: Linda
authors.initials: L
authors.lastname: Pescatello
authors.forename: Linda
authors.initials: L
authors.lastname: Bausserman
authors.forename: Niall
authors.initials: N
authors.lastname: Moyna
mesh_terms: D000328:Adult; D015308:Anaerobic Threshold / Q000502:physiology*; D001057:Apolipoproteins E / Q000235:genetics*; D001823:Body Composition / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004032:Diet; D004734:Energy Metabolism / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D008049:Lipase / Q000378:metabolism; D008055:Lipids / Q000097:blood*; D008071:Lipoprotein Lipase / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000502:physiology*; D010809:Physical Fitness / Q000502:physiology*
chemical_list: D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005230:Fatty Acids, Nonesterified; D008055:Lipids; D008074:Lipoproteins; D008049:Lipase; D008071:Lipoprotein Lipase