Journal
JOURNAL OF LIPID RESEARCH
Volume 52, Issue 8, Pages 1575-1582Publisher
ELSEVIER
DOI: 10.1194/jlr.P015867
Keywords
Angptl4; heritability; twin pairs; obesity-discordant monozygotic twins
Categories
Funding
- National Institute for Health and Welfare
- Finnish Foundation for Cardiovascular Research
- Magnus Ehrnrooth Foundation
- Finska Lakaresallskapet
- Paulo Foundation
- Oskar Oflunds Stiftelse
- Helsinki University Central Hospital
- Academy of Finland
- Jalmari and Rauha Ahokas
- Yrjo Jahnsson
- Gyllenberg
- Biomedicum Helsinki
- Novo Nordisk Foundations
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Animal studies have suggested that angiopoietin-like 4 (Angptl4) regulates adiposity through central and peripheral mechanisms. The aim of this study was to investigate whether serum concentration and adipose tissue expression of Angptl4 are associated with obesity-related parameters in humans. Altogether, 75 dizygotic (DZ) and 46 monozygotic (MZ) twin pairs were studied, from the FinnTwin12 and FinnTwin16 cohorts. Among the MZ pairs, 21 were discordant for body mass index (BMI) (intra-pair BMI-difference >2.5 kg/m(2), age 23-33 years). Serum Angptl4 (s-Angptl4) levels were measured by ELISA, and adipose tissue gene expression was analyzed by genome-wide transcript profiling. In MZ twin pairs discordant for BMI, s-Angptl4 and adipose tissue ANGPTL4 mRNA (at-ANGPTL4) levels were significantly decreased (P = 0.04 and P = 0.03, respectively) in obese twins as compared with their nonobese cotwins. In all twins, intra-pair differences in s-Angptl4 levels were inversely correlated with intra-pair differences in BMI (r = -0.27, P = 0.003). In individual MZ twins, at-ANGPTL4 expression was inversely correlated with BMI (r = -0.44, P = 0.001) and positively correlated with at-LIPE (r = 0.24, P = 0.01) and at-ABHD5 (r = 0.41, P = 0.005) expression. Our results demonstrated that variation in Angptl4 concentration was only modestly accounted for by genetic factors and suggest a role for Angptl4 in acquired obesity in humans.-Robciuc, M. R., J. Naukkarinen, A. Ortega-Alonso, H. Tyynismaa, T. Raivio, A. Rissanen, J. Kaprio, C. Ehnholm, M. Jauhiainen, and K. H. Pietilainen. Serum angiopoietin-like 4 protein
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