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

• Published in: The journal of clinical endocrinology and metabolism Vol. 93; no. 4; pp. 1497 - 1500
• Main Authors: Thamer, Claus, Machann, Jürgen, Stefan, Norbert, Schäfer, Silke A, Machicao, Fausto, Staiger, Harald, Laakso, Markku, Böttcher, Michael, Claussen, Claus, Schick, Fritz, Fritsche, Andreas, Haring, Hans-Ulrich
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.04.2008; Copyright by The Endocrine Society
• Subjects: Adiposity; Adult; Aged; Biological and medical sciences; Body Composition; Diet; Endocrinopathies; Exercise; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Humans; Insulin Resistance; Life Style; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Medical sciences; Middle Aged; Polymorphism, Single Nucleotide; PPAR delta - genetics; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Obesity; Nutrition; Magnetic resonance; Nutrition disorder; Variations; Metabolic diseases; Change; Nuclear magnetic resonance imaging; Body composition; Medical imagery; Whole body; Endocrinology; Nutritional status; Life style
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2007-1209

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