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Visceral obesity modulates the impact of apolipoprotein C3 gene variants on liver fat content

International Journal of Obesity volume 36, pages 774–782 (2012)Cite this article

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 1H-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.

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Acknowledgements

We would like to thank all the participants for their cooperation and Roman Werner, Melanie Weisser, Alke Guirguis and Mareike Walenta and the phenotyping team for their help in collecting the data. The study was supported by grants from the Deutsche Forschungsgemeinschaft (KFO 114 and a Heisenberg-Grant to NS, STE 1096/1-1), the European Community's FP6 EUGENE2 (LSHM-CT-2004-512013) and the German Federal Ministry of Education and Research (DLR01GI0925).

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Author notes

  1. A Peter and K Kantartzis: These authors are contributed equally to this work.

Authors and Affiliations

  1. Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen, Member of the Deutsches Zentrum für Diabetesforschung (DZD), Tübingen, Germany

    A Peter, K Kantartzis, F Machicao, A Fritsche, H-U Häring & N Stefan

  2. Section on Experimental Radiology, University of Tübingen, Tübingen, Germany

    J Machann & F Schick

  3. Department of General, Visceral and Transplant Surgery, University of Tübingen, Tübingen, Germany

    S Wagner, S Templin, I Königsrainer & A Königsrainer

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Correspondence to N Stefan.

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Peter, A., Kantartzis, K., Machicao, F. et al. Visceral obesity modulates the impact of apolipoprotein C3 gene variants on liver fat content. Int J Obes 36, 774–782 (2012). https://doi.org/10.1038/ijo.2011.154

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