Variations in PPARD determine the change in body composition during lifestyle intervention

TY - JOUR

T1 - Variations in PPARD determine the change in body composition during lifestyle intervention

T2 - a whole-body magnetic resonance study

AU - Thamer, Claus

AU - Machann, Jürgen

AU - Stefan, Norbert

AU - Schäfer, Silke A

AU - Machicao, Fausto

AU - Staiger, Harald

AU - Laakso, Markku

AU - Böttcher, Michael

AU - Claussen, Claus

AU - Schick, Fritz

AU - Fritsche, Andreas

AU - Haring, Hans-Ulrich

PY - 2008/4/1

Y1 - 2008/4/1

N2 - 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.

AB - 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.

KW - Adiposity

KW - Adult

KW - Aged

KW - Body Composition

KW - Diet

KW - Exercise

KW - Female

KW - Humans

KW - Insulin Resistance

KW - Life Style

KW - Magnetic Resonance Imaging

KW - Magnetic Resonance Spectroscopy

KW - Male

KW - Middle Aged

KW - PPAR delta

KW - Polymorphism, Single Nucleotide

U2 - 10.1210/jc.2007-1209

DO - 10.1210/jc.2007-1209

M3 - SCORING: Journal article

C2 - 18252792

VL - 93

SP - 1497

EP - 1500

JO - J CLIN ENDOCR METAB

JF - J CLIN ENDOCR METAB

SN - 0021-972X

IS - 4

ER -