title: Gene-nutrient interactions on the phosphoenolpyruvate carboxykinase influence insulin sensitivity in metabolic syndrome subjects.
abstract: OBJECTIVE
  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 LIPGENE 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.
authors.affiliation: Lipid and Atherosclerosis Research Unit, IMIBIC, Reina Sofia University Hospital, University of Cordoba, Avda. Menéndez Pidal, 14004 Córdoba, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Perez-Martinez
authors.forename: Antonio
authors.initials: A
authors.lastname: Garcia-Rios
authors.forename: Javier
authors.initials: J
authors.lastname: Delgado-Lista
authors.forename: Ingrid M F
authors.initials: IM
authors.lastname: Gjelstad
authors.forename: James
authors.initials: J
authors.lastname: Gibney
authors.forename: Beata
authors.initials: B
authors.lastname: Kieć-Wilk
authors.forename: Antonio
authors.initials: A
authors.lastname: Camargo
authors.forename: Olfa
authors.initials: O
authors.lastname: Helal
authors.forename: Brita
authors.initials: B
authors.lastname: Karlström
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Blaak
authors.forename: Wendy
authors.initials: W
authors.lastname: Hall
authors.forename: Ulf
authors.initials: U
authors.lastname: Risérus
authors.forename: Aldona
authors.initials: A
authors.lastname: Dembińska-Kieć
authors.forename: Catherine
authors.initials: C
authors.lastname: Defoort
authors.forename: Wim H M
authors.initials: WH
authors.lastname: Saris
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lovegrove
authors.forename: Christian A
authors.initials: CA
authors.lastname: Drevon
authors.forename: Helen M
authors.initials: HM
authors.lastname: Roche
authors.forename: Jose
authors.initials: J
authors.lastname: Lopez-Miranda
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D000368:Aged; D000483:Alleles; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D003430:Cross-Sectional Studies; D004041:Dietary Fats / Q000008:administration & dosage; D005215:Fasting; D015525:Fatty Acids, Omega-3 / Q000097:blood; D005260:Female; D059647:Gene-Environment Interaction; D056426:Genetic Loci; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D000078790:Insulin Secretion; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D016014:Linear Models; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D016032:Randomized Controlled Trials as Topic
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; C521898:PCK1 protein, human; D010729:Phosphoenolpyruvate Carboxykinase (GTP)