Effect of pre-existing maternal obesity, gestational diabetes and adipokines on the expression of genes involved in lipid metabolism in adipose tissue

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.

Keywords: ASCL1; Cytokines; DAG; DGAT; FABP; FABPpm; FASN; FATP; FFA; Fatty acid transport; Fatty acid uptake; GDM; HSL; LPL; LXR; MAG; MGAT; MGLL; NGT; PNPLA2; PPAR; Pregnancy; RXR; SREBP1c; TAG; Transcription factors; acyl-CoA synthetase long-chain family member 1; adipose triglyceride lipase; diacylglycerol; diacylglycerol acyltransferases; fatty acid binding protein; fatty acid synthase; fatty acid transport protein; free fatty acid; gestational diabetes mellitus; hormone-sensitive lipase; lipoprotein lipase; liver X receptor; monoacyglycerol acyltransferases; monoacylglycerol.; monoglyceride lipase; normal glucose tolerant; plasma membrane fatty acid binding protein; proliferator activated receptor; qRT-PCR; quantitative RT-PCR; retinoid X receptor; sterol regulatory element binding protein; triacylglyceride.