M T Kaartinen1,2, M Arora3, S Heinonen4, A Hang3, A Barry5,6, J Lundbom7, A Hakkarainen7, N Lundholm7, A Rissanen4, J Kaprio8,9, K H Pietiläinen4,7. 1. Faculty of Medicine (Division of Experimental Medicine), McGill University, Montreal, QC, Canada. mari.kaartinen@mcgill.ca. 2. Faculty of Dentistry (Biomedical Sciences), McGill University, Montreal, QC, Canada. mari.kaartinen@mcgill.ca. 3. Faculty of Medicine (Division of Experimental Medicine), McGill University, Montreal, QC, Canada. 4. Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland. 5. Departments of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada. 6. Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada. 7. Obesity Center, Abdominal Center, Endocrinology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. 8. Department of Public Health, Finnish Twin Cohort Study, University of Helsinki, Helsinki, Finland. 9. Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
Abstract
OBJECTIVE: F13A1/FXIII-A transglutaminase has been linked to adipogenesis in cells and to obesity in humans and mice, however, its role and associated molecular pathways in human acquired excess weight have not been explored. METHODS: We examined F13A1 expression and association to human weight gain in weight-discordant monozygotic twins (Heavy-Lean difference (ΔWeight, 16.8 kg ± 7.16 for n = 12). The twin pairs were examined for body composition (by dual-energy X-ray absorptiometry), abdominal body fat distribution (by magnetic resonance imaging), liver fat content (by magnetic resonance spectroscopy), circulating adipocytokines, leptin and adiponectin, as well as serum lipids. Affymetrix full transcriptome mRNA analysis was performed from adipose tissue and adipocyte-enriched fractions from subcutaneous abdominal adipose tissue biopsies. F13A1 differential expression between the heavy and lean co-twins was examined and its correlation transcriptome changes between co-twins were performed. RESULTS: F13A1 mRNA showed significant increase in adipose tissue (p < 0.0001) and an adipocyte-enriched fraction (p = 0.0012) of the heavier co-twin. F13A1 differential expression in adipose tissue (Heavy-Lean ΔF13A1) showed significant negative correlation with circulating adiponectin (p = 0.0195) and a positive correlation with ΔWeight (p = 0.034), ΔBodyFat (0.044) and ΔAdipocyte size (volume, p = 0.012;) in adipocyte-enriched fraction. A whole transcriptome-wide association study (TWAS) on ΔF13A1 vs weight-correlated ΔTranscriptome identified 182 F13A1-associated genes (r > 0.7, p = 0.05) with functions in several biological pathways including cell stress, inflammatory response, activation of cells/leukocytes, angiogenesis and extracellular matrix remodeling. F13A1 did not associate with liver fat accumulation. CONCLUSIONS: F13A1 levels in adipose tissue increase with acquired excess weight and associate with pro-inflammatory, cell stress and tissue remodeling pathways. This supports its role in expansion and inflammation of adipose tissue in obesity.
OBJECTIVE: F13A1/FXIII-A transglutaminase has been linked to adipogenesis in cells and to obesity in humans and mice, however, its role and associated molecular pathways in human acquired excess weight have not been explored. METHODS: We examined F13A1 expression and association to human weight gain in weight-discordant monozygotic twins (Heavy-Lean difference (ΔWeight, 16.8 kg ± 7.16 for n = 12). The twin pairs were examined for body composition (by dual-energy X-ray absorptiometry), abdominal body fat distribution (by magnetic resonance imaging), liver fat content (by magnetic resonance spectroscopy), circulating adipocytokines, leptin and adiponectin, as well as serum lipids. Affymetrix full transcriptome mRNA analysis was performed from adipose tissue and adipocyte-enriched fractions from subcutaneous abdominal adipose tissue biopsies. F13A1 differential expression between the heavy and lean co-twins was examined and its correlation transcriptome changes between co-twins were performed. RESULTS: F13A1 mRNA showed significant increase in adipose tissue (p < 0.0001) and an adipocyte-enriched fraction (p = 0.0012) of the heavier co-twin. F13A1 differential expression in adipose tissue (Heavy-Lean ΔF13A1) showed significant negative correlation with circulating adiponectin (p = 0.0195) and a positive correlation with ΔWeight (p = 0.034), ΔBodyFat (0.044) and ΔAdipocyte size (volume, p = 0.012;) in adipocyte-enriched fraction. A whole transcriptome-wide association study (TWAS) on ΔF13A1 vs weight-correlated ΔTranscriptome identified 182 F13A1-associated genes (r > 0.7, p = 0.05) with functions in several biological pathways including cell stress, inflammatory response, activation of cells/leukocytes, angiogenesis and extracellular matrix remodeling. F13A1 did not associate with liver fat accumulation. CONCLUSIONS: F13A1 levels in adipose tissue increase with acquired excess weight and associate with pro-inflammatory, cell stress and tissue remodeling pathways. This supports its role in expansion and inflammation of adipose tissue in obesity.
Authors: Richard L Eckert; Mari T Kaartinen; Maria Nurminskaya; Alexey M Belkin; Gozde Colak; Gail V W Johnson; Kapil Mehta Journal: Physiol Rev Date: 2014-04 Impact factor: 37.312
Authors: Jussi Naukkarinen; Ida Surakka; Kirsi H Pietiläinen; Aila Rissanen; Veikko Salomaa; Samuli Ripatti; Hannele Yki-Järvinen; Cornelia M van Duijn; H-Erich Wichmann; Jaakko Kaprio; Marja-Riitta Taskinen; Leena Peltonen Journal: PLoS Genet Date: 2010-06-03 Impact factor: 5.917