Endurance training alleviates PRKCQ genotype-related metabolic abnormalities

Protein kinase C theta (PRKCQ) knock-out mice manifest decreased energy expenditure as compared to wild-type mice due to reduced spontaneous physical activity and they develop obesity and insulin resistance on a high-fat diet. PURPOSE: We tested the hypothesis that DNA sequence variation in the human PRKCQ gene locus is associated with adiposity and plasma insulin phenotypes in the sedentary state and in response to endurance training in the HERITAGE Family Study. METHODS: Fasting plasma insulin, MINMOD-derived insulin sensitivity (SI), body composition (underwater weighing), and abdominal visceral fat (AVF; CT scan) were measured in the sedentary state (baseline) and after a 20-week endurance training program in 247 Blacks and 476 Whites. Nine PRKCQ tagSNPs were genotyped using the FP-TDI method. RESULTS: In Blacks, both baseline fasting insulin (p<0.022; adjusted for age, sex, and BMI) and AVF (p<0.001; adjusted for age, sex, and fat mass) were associated with two SNPsatthe5'endofthegene(rs541709, rs571715), whereas a SNP in intron 3 (rs510745) was associated with baseline SI (p=0.005). For insulin and SI, the associations were observed in offspring (p<0.0006) but not in parents (genotype-by-generation interactions p<0.05). The same 5′ SNPs were associated with AVF and fasting insulin training responses in Black offspring (p<0.004): the common allele homozygotes having the highest AVF and fasting insulin levels at baseline but showing the greatest training-induced reductions in both traits. In White offspring, both rs541709 (p=0.045) and rs510745 (p=0.025), as well as rs677986 in intron 15 (p=0.007) were associated with fasting insulin at baseline. Baseline AVF was not associated with the PRKCQ SNPs in Whites. However, the Leu330Pro variant (rs2236379) in exon 8 showed significant association with training-induced changes in AVF (p=0.022). The PRKCQ SNPs were not associated with body composition traits in either ethnicity. CONCLUSION: Our data suggest that DNA sequence variation at the human PRKCQ locus increases the risk of accumulating intra-abdominal fat and having elevated fasting insulin levels in sedentary young adults. However, regular physical activity seems to counteract to some extent both PRKCQ locus -related metabolic disturbances.