Does peroxisome proliferator-activated receptor γ genotype (Pro12ala) modify the association of physical activity and dietary fat with fasting insulin level?

• Published in: Metabolism, clinical and experimental clinical and experimental, 2004, Vol.53 (1), p.11-16
• Main Authors: Franks, P.W, Luan, J, Browne, P.O, Harding, A.-H, O’Rahilly, S, Chatterjee, V.K.K, Wareham, N.J
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alanine; Alleles; Biological and medical sciences; Body Mass Index; Cohort Studies; Diabetes. Impaired glucose tolerance; Diet Records; Dietary Fats - administration & dosage; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Energy Metabolism; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Exercise - physiology; Fasting; Fatty Acids - administration & dosage; Fatty Acids, Unsaturated - administration & dosage; Female; Genotype; Heart Rate; Humans; Insulin - blood; Male; Medical sciences; Middle Aged; Polymorphism, Genetic; Proline; Prospective Studies; Protein Isoforms - genetics; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - physiology; Surveys and Questionnaires; Transcription Factors - genetics; Transcription Factors - physiology
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2003.08.005

Peroxisome proliferator-activated receptor γ (PPARγ) has a role in controlling adipogenesis and insulin sensitivity. Previous studies have suggested that a common polymorphism (Pro12Ala) in the PPARγ-2 isoform of this gene may be associated with markers of insulin resistance. We have previously shown that in combination, the relationships with fasting insulin of dietary polyunsaturated to saturated fatty acid ratio (P:S ratio) and physical activity are additive. We have also demonstrated that the association between P:S ratio and fasting insulin level is modified by the Pro12Ala genotype. The purpose of the present study was to investigate whether the Pro12Ala genotype modified the combined relationships of P:S ratio and physical activity level (PAL) on fasting insulin concentration. A population-based cohort of 506 Caucasian men and women aged 31 to 71 years was genotyped for the Pro12Ala polymorphism. P:S ratio was assessed by food-frequency questionnaire (FFQ) and PAL was estimated from 4 days of free-living heart rate monitoring following individual calibration of heart rate against energy expenditure during an exercise stress test. The combined associations of PAL and P:S ratio on fasting insulin level were examined stratified by Pro12Ala genotypes in a dominant model for the Ala allele. Among Pro allele homozygotes, there was no interaction between PAL and P:S ratio on fasting insulin ( P = .929). However, in carriers of the Ala allele the association of P:S ratio with fasting insulin was modified by activity level (interaction P = 0.038). In those who were inactive and carried the Ala allele, the age-, sex-, and body mass-adjusted relationship between P:S ratio and log insulin was not significant (β = −0.03, P = .93). In contrast, in physically active Ala carriers, the association of P:S ratio with log fasting insulin was highly significant (β = −0.93, P = .004). In conclusion, this study examined the modification by PPARγ genotype of the association between energy expenditure, P:S ratio, and fasting insulin level, a measure of insulin resistance. These data show that in Pro allele homozygotes the combined associations of P:S ratio and PAL are additive. In contrast, in Ala allele carriers, PAL modifies the association between P:S ratio and fasting insulin level in a multiplicative manner.