title: Visceral obesity modulates the impact of apolipoprotein C3 gene variants on liver fat content.
abstract: OBJECTIVE
  It has not been solved whether subjects carrying the minor alleles of the -455T>C or -482C>T single nucleotide polymorphisms (SNPs) in the apolipoprotein-C3-gene (APOC3) have an increased risk for developing fatty liver and insulin resistance. We investigated the relationships of the SNPs with hepatic APOC3 expression and hypothesized that visceral obesity may modulate the effects of these SNPs on liver fat and insulin sensitivity (IS).
  
  
  METHODS
  APOC3 mRNA expression and triglyceride content were determined in liver biopsies from 50 subjects. In a separate group (N=330) liver fat was measured by (1)H-magnetic resonance spectroscopy. IS was estimated during an oral glucose tolerance test (OGTT) and the euglycemic, hyperinsulinemic clamp (N=222).
  
  
  RESULTS
  APOC3 mRNA correlated positively with triglyceride content in liver biopsies (r=0.29, P=0.036). Carriers of the minor alleles (-455C and -482T) tended to have higher hepatic APOC3 mRNA expression (1.80 (0.45-3.56) vs 0.77 (0.40-1.64), P=0.09), but not higher triglyceride content (P=0.76). In 330 subjects the genotype did not correlate with liver fat (P=0.97) or IS (OGTT: P=0.41; clamp: P=0.99). However, a significant interaction of the genotype with waist circumference in determining liver fat was detected (P=0.02) in which minor allele carriers had higher liver fat only in the lowest tertile of waist circumference (P=0.01). In agreement, during a 9-month lifestyle intervention the minor allele carriers of the SNP -482C>T in the lowest tertile also had less decrease in liver fat (P=0.04).
  
  
  CONCLUSIONS
  APOC3 mRNA expression is increased in fatty liver and is regulated by SNPs in APOC3. The impact of the APOC3 SNPs on fatty liver is small and depends on visceral obesity.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen, Otfried-Müller-Street 10, Tübingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Peter
authors.forename: K
authors.initials: K
authors.lastname: Kantartzis
authors.forename: F
authors.initials: F
authors.lastname: Machicao
authors.forename: J
authors.initials: J
authors.lastname: Machann
authors.forename: S
authors.initials: S
authors.lastname: Wagner
authors.forename: S
authors.initials: S
authors.lastname: Templin
authors.forename: I
authors.initials: I
authors.lastname: Königsrainer
authors.forename: A
authors.initials: A
authors.lastname: Königsrainer
authors.forename: F
authors.initials: F
authors.lastname: Schick
authors.forename: A
authors.initials: A
authors.lastname: Fritsche
authors.forename: H-U
authors.initials: HU
authors.lastname: Häring
authors.forename: N
authors.initials: N
authors.lastname: Stefan
mesh_terms: D053305:Apolipoprotein C-III / Q000097:blood / Q000235:genetics*; D005234:Fatty Liver / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008099:Liver / Q000473:pathology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D014280:Triglycerides / Q000097:blood*
chemical_list: D053305:Apolipoprotein C-III; D014280:Triglycerides