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


METHODS
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.


CONCLUSIONS
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.
Thamer
Claus
C
Department of Endocrinology, Metabolism, Clinical Chemistry, Nephrology, and Angiology, Medical Clinic, Eberhard-Karls-University, 72076 Tuebingen, Germany.
Machann
Jürgen
J
Stefan
Norbert
N
Schäfer
Silke A
SA
Machicao
Fausto
F
Staiger
Harald
H
Laakso
Markku
M
Böttcher
Michael
M
Claussen
Claus
C
Schick
Fritz
F
Fritsche
Andreas
A
Haring
Hans-Ulrich
HU
D050154:Adiposity; D000328:Adult; D000368:Aged; D001823:Body Composition; D004032:Diet; D015444:Exercise; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008019:Life Style; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D047494:PPAR delta / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D047494:PPAR delta