Gene-nutrient interactions on the phosphoenolpyruvate carboxykinase influence insulin sensitivity in metabolic syndrome subjects
2013 (English)In: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 32, no 4, 630-635 p.Article in journal (Refereed) Published
Background & aims: Genetic background may interact with habitual dietary fat composition, and affect development of the metabolic syndrome (MetS). The phosphoenolpyruvate carboxykinase gene (PCK1) plays a significant role regulating glucose metabolism, and fatty acids are key metabolic regulators, which interact with transcription factors and influence glucose metabolism. We explored genetic variability at the PCK1 gene locus in relation to degree of insulin resistance and plasma fatty acid levels in MetS subjects. Moreover, we analyzed the PCK1 gene expression in the adipose tissue of a subgroup of MetS subjects according to the PCK1 genetic variants. Methods: Insulin sensitivity, insulin secretion, glucose effectiveness, plasma concentrations of C-peptide, fatty acid composition and three PCK1 tag-single nucleotide polymorphisms (SNPs) were determined in 443 MetS participants in the UPGENE cohort. Results: The rs2179706 SNP interacted with plasma concentration of n - 3 polyunsaturated fatty acids (n - 3 PUFA), which were significantly associated with plasma concentrations of fasting insulin, peptide C, and HOMA-IR. Among subjects with n - 3 PUFA levels above the population median, carriers of the C/C genotype exhibited lower plasma concentrations of fasting insulin (P = 0.036) and HOMA-IR (P = 0.019) as compared with C/C carriers with n - 3 PUFA below the median. Moreover, homozygous C/C subjects with n - 3 PUFA levels above the median showed lower plasma concentrations of peptide C as compared to individuals with the T-allele (P = 0.006). Subjects carrying the T-allele showed a lower gene PCK1 expression as compared with carriers of the C/C genotype (P = 0.015). Conclusions: The PCK1 rs2179706 polymorphism interacts with plasma concentration of n - 3 PUFA levels modulating insulin resistance in MetS subjects.
Place, publisher, year, edition, pages
2013. Vol. 32, no 4, 630-635 p.
HOMA-IR, Metabolic syndrome, n-3 polyunsaturated fatty acids, PCK1 gene, Adipose tissue, Nutrigenetics
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-204832DOI: 10.1016/j.clnu.2012.10.003ISI: 000321726300021OAI: oai:DiVA.org:uu-204832DiVA: diva2:640343
De två (2) första författarna delar förstaförfattarskapet.
De två (2) sista författarna delar sistaförfattarskapet.2013-08-132013-08-122013-08-13Bibliographically approved