Martha Lappas1. 1. Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia; Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia. Electronic address: mlappas@unimelb.edu.au.
Abstract
OBJECTIVE: To determine the effect of maternal obesity, gestational diabetes mellitus (GDM) and adipokines on the expression of genes involved in fatty acid uptake, transport, synthesis and metabolism. MATERIALS/ METHODS: Human subcutaneous and omental adipose tissues were obtained from lean, overweight and obese normal glucose tolerant (NGT) women and women with GDM. Quantitative RT-PCR (qRT-PCR) was performed to determine the level of expression. Adipose tissue explants were performed to determine the effect of the adipokines TNFα, IL-1β and leptin on adipose tissue gene expression. RESULTS: Pre-existing maternal obesity and GDM are associated with decreased expression in genes involved in fatty acid uptake and intracellular transport (LPL, FATP2, FATP6, FABPpm and ASCL1), triacylglyceride (TAG) biosynthesis (MGAT1,7 MGAT2 and DGAT1), lipogenesis (FASN) and lipolysis (PNPLA2, HSL and MGLL). Decreased gene expression was also observed for the transcription factors involved in lipid metabolism (LXRα, PPARα, PPARδ, PPARγ, RXRα and SREBP1c). On the other hand, the gene expression of the adipokines TNFα, IL-1β and or leptin was increased in adipose tissue from obese and GDM women. Functional in vitro studies revealed that these adipokines decreased the gene expression of LPL, FATP2, FATP6, ASCL1, PNPLA2, PPARδ, PPARγ and RXRα. CONCLUSIONS: Pregnancies complicated by pre-existing maternal obesity and GDM are associated with abnormal adipose tissue lipid metabolism, which may play a role in the pathogenesis of these diseases.
OBJECTIVE: To determine the effect of maternal obesity, gestational diabetes mellitus (GDM) and adipokines on the expression of genes involved in fatty acid uptake, transport, synthesis and metabolism. MATERIALS/ METHODS:Human subcutaneous and omental adipose tissues were obtained from lean, overweight and obese normal glucose tolerant (NGT) women and women with GDM. Quantitative RT-PCR (qRT-PCR) was performed to determine the level of expression. Adipose tissue explants were performed to determine the effect of the adipokines TNFα, IL-1β and leptin on adipose tissue gene expression. RESULTS: Pre-existing maternal obesity and GDM are associated with decreased expression in genes involved in fatty acid uptake and intracellular transport (LPL, FATP2, FATP6, FABPpm and ASCL1), triacylglyceride (TAG) biosynthesis (MGAT1,7 MGAT2 and DGAT1), lipogenesis (FASN) and lipolysis (PNPLA2, HSL and MGLL). Decreased gene expression was also observed for the transcription factors involved in lipid metabolism (LXRα, PPARα, PPARδ, PPARγ, RXRα and SREBP1c). On the other hand, the gene expression of the adipokines TNFα, IL-1β and or leptin was increased in adipose tissue from obese and GDM women. Functional in vitro studies revealed that these adipokines decreased the gene expression of LPL, FATP2, FATP6, ASCL1, PNPLA2, PPARδ, PPARγ and RXRα. CONCLUSIONS: Pregnancies complicated by pre-existing maternal obesity and GDM are associated with abnormal adipose tissue lipid metabolism, which may play a role in the pathogenesis of these diseases.
Authors: Linn Gillberg; Alexander Perfilyev; Charlotte Brøns; Martin Thomasen; Louise G Grunnet; Petr Volkov; Fredrik Rosqvist; David Iggman; Ingrid Dahlman; Ulf Risérus; Tina Rönn; Emma Nilsson; Allan Vaag; Charlotte Ling Journal: Diabetologia Date: 2016-01-11 Impact factor: 10.122