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Variations in PPARD Determine the Change in Body Composition during Lifestyle Intervention: A Whole-Body Magnetic Resonance Study

Department of Endocrinology, Metabolism, Clinical Chemistry, Nephrology, and Angiology (C.T., N.S., S.A.S., F.M., H.S., A.F., H.-U.H.), Medical Clinic, Eberhard-Karls-University, 72076 Tuebingen, Germany; Department of Diagnostic Radiology (J.M., M.B., C.C., F.S.), Section on Experimental Radiology, Eberhard-Karls-University, 72076 Tübingen, Germany; and Department of Medicine, University of Kuopio (M.L.), KI-70210 Kuopio, Finland

Address all correspondence and requests for reprints to: Hans-Ulrich Haring, M.D., Medical Clinic, Department of Internal Medicine IV, Otfried-Müller-Str. 10, 72076 Tübingen, Germany. E-mail: hans-ulrich.haering{at}med.uni-tuebingen.de.

Context: We recently demonstrated that single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor- 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.

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