SFEBES2018 Poster Presentations Obesity & metabolism (24 abstracts)
Angiopoietin-like ptotein 4 and 8 (ANGPTL4 and ANGPTL8) in human fetal liver are dysregulated by in utero exposure to maternal smoking
Chiara Talia 1 , Panagiotis Filis 1 , Ugo Soffientini 2 , Baltasar Lucendo-Villarin 3 , Alex Douglas 1 , David Hay 4 , Sophie Shaw 1 , John Iredale 5 , Madeleine Swortwood 6 , Marilyn Huestis 6 , Michelle Bellingham 2 , Lisa Connolly 7 , Peter O’Shaughnessy 2 & Paul Fowler 1
1Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK; 2University of Glasgow, Institute of Biodiversity, Animal Health and Comparative Medicine, Glasgow, UK; 3University of Edinburgh, Medical Research Council Centre for Regenerative Medicine, Edinburgh, UK; 4University of Edinburgh, Medical Research Council Centre for Regenerative Medicine, Edinburgh, UK; 5University of Bristol, Senate House, Bristol, UK; 6National Institutes of Health, Chemistry and Drug Metabolism, Intramural Research Program National Institute on Drug Abuse, Baltimore, USA; 7Queen’s University Belfast, Institute for Global Food Security, Belfast, UK.
Introduction: Angiopoietin-like proteins (ANGPTLs) are a family of 8 glycoproteins with pleiotropic effects in metabolism, angiogenesis, inflammation and cancer. ANGPTL3, 4 and 8 play major roles in regulating lipid levels, via inhibition of lipoprotein lipase. Increased serum ANGPTL3, 4, 8 levels are associated with obesity, diabetes, metabolic syndrome and fatty liver. Furthermore, cord blood ANGPTL8 is higher than in maternal serum, suggesting a role in fetal development and growth. However, human fetal studies are lacking.
Aim: To investigate ANGPTLs in the human fetal liver transcriptome.
Methods: 80 human fetal livers from elective terminations of normal pregnancies (12–19 gestation weeks), were collected (NHS Grampian Research Ethics Committees, REC 04/S0802/21) and RNA extracted. 76 bp single end RNA sequencing reads were then produced (Illumina NextSeq platform). Reads were aligned to the human reference genome and quantified at gene regions. Significant differentially expressed genes were identified using a generalised linear model with a three-way interaction between fetal sex, fetal age and maternal smoking status (confirmed by measuring fetal cotinine).
Results: All ANGPTLs, with the exception of ANGPTL5 and ANGPTL7, were robustly detected in all samples. ANGPTL4 and ANGPTL8 exhibited significant changes in the three-way interaction model (P < 0.001). ANGPTL4 was significantly upregulated (3-fold) in older smoke-exposed males (>17 gestation weeks). ANGPTL8 was significantly higher in 14–16 gestation weeks smoke-exposed females (5-fold) and in >17 gestation weeks smoke-exposed males (7-fold).
Conclusions: We report, for the first time, ANGPTLs transcript in human fetal livers across the second trimester of gestation. In utero exposure to cigarette smoke resulted in marked sex- and age-specific changes in ANGPTL4 and ANGPTL8. Maternal smoking is associated with an increased risk of obesity and metabolic syndrome in offspring. Therefore, we suggest that ANGPTL dysregulation during fetal life may play a role in adverse metabolic reprogramming.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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