Variations in PPARD determine the change in body composition during lifestyle intervention: a whole-body magnetic resonance study

J Clin Endocrinol Metab. 2008 Apr;93(4):1497-500. doi: 10.1210/jc.2007-1209. Epub 2008 Feb 5.


Context: We recently demonstrated that single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor-delta gene (PPARD), i.e. rs1053049, rs6902123, and rs2267668, affect the improvement of mitochondrial function, aerobic physical fitness, and insulin sensitivity by lifestyle intervention (LI).

Objective: The objective of the study was to determine whether the aforementioned PPARD SNPs influence the change in body composition and ectopic fat storage during LI.

Design: A total of 156 subjects at an increased risk for type 2 diabetes were genotyped for rs1053049, rs6902123, and rs2267668 and participated in a LI program. Body fat depots, ectopic liver fat, and muscle volume of the leg were quantified using magnetic resonance spectroscopy and imaging.

Results: With regard to body composition, carriers of the minor SNP alleles displayed reduced responses to LI, i.e. LI-induced reduction in adipose tissue mass (nonvisceral adipose tissue: rs1053049, P = 0.02; rs2267668, P = 0.04; visceral adipose tissue: rs1053049, P = 0.01) and hepatic lipids (rs1053049, P = 0.04; rs6902123, P = 0.001; independent of changes in adiposity) as well as LI-induced increase in relative muscle volume of the leg (rs1053049, P = 0.003; rs2267668, P = 0.009) were less pronounced in homo- and heterozygous carriers of the minor alleles as compared with homozygous carriers of the major alleles.

Conclusion: SNPs rs1053049, rs6902123, and rs2267668 in PPARD affect LI-induced changes in overall adiposity, hepatic fat storage, and relative muscle mass. Our findings provide a mechanistic explanation for the involvement of these genetic variations in the development of insulin resistance and type 2 diabetes.

MeSH terms

  • Adiposity
  • Adult
  • Aged
  • Body Composition*
  • Diet
  • Exercise
  • Female
  • Humans
  • Insulin Resistance
  • Life Style*
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • PPAR delta / genetics*
  • Polymorphism, Single Nucleotide*


  • PPAR delta