Hypoxia regulates the expression of fatty acid–binding proteins in primary term human trophoblasts

Abstract

Objective-Fatty acids (FA) are essential for fetal development. Cellular FA uptake is modulated by fatty acid binding proteins (FABPs). We hypothesized that hypoxia regulates the expression of FABPs in human trophoblasts.Study design-Primary term human trophoblasts were cultured for 72 h in either standard (O 2 = 20%) or hypoxic (O 2 < 1%) conditions. FABP expression was interrogated using PCR and western immunoblotting. Trophoblast lipid droplets were examined using BODIPY 493/503 staining.Results-We detected the expression of FABP1, 3, 4, 5 and pm, but not FABP2 or FABP6-9 subtypes in trophoblasts. Exposure to hypoxia markedly increased lipid droplet accumulation in trophoblasts. Consistent with this observation, hypoxia enhanced the expression of FABP1, 3 and 4. Lastly, agonists of peroxisome proliferator activated receptor-γ (PPARγ) enhanced the expression of FABP1 and 4 in trophoblasts.Conclusions-Hypoxia enhances the expression of FABP1, 3 and 4 in term human trophoblasts, suggesting that FABPs support fat accumulation in the hypoxic placenta.

Regulation of fatty acid binding proteins by hypoxia inducible factors 1α and 2α in the placenta: Relevance to pre-eclampsia

“…Our findings are in keeping with those of Biron-Shental et al [7] who described an increase in FABP1, FABP3 and FABP4 protein expressions in primary cultured trophoblast cells in response to 48 h of exposure to gaseous hypoxia (O 2 o 1%). Mishima et al [8] showed that FATP2 mRNA levels were increased in primary cultured trophoblasts cultured for 48 h in gaseous hypoxia (O 2 o 1%).…”

“…2A). CoCl 2 is a well-described hypoxiamimetic agent [7,12,14] but also activates the nuclear transcription factor NF-κB [15]. There are two putative κB elements within the FABP3 gene at À 834 and À 825 bp that are presumably responsible for this increase in luciferase activity (data not shown).…”

“…These include three intracellular liver, heart and adipocyte fatty acid binding proteins (FABP1, FABP3, and FABP4 respectively) and membrane associated fatty acid transport protein 2/very long chain acyl CoA synthetase 1 (FATP2) [6]. The protein levels of FABP1, FABP3 and FABP4 increase in hypoxic human trophoblasts [7]. The mRNA levels of FATP2 increase in primary human trophoblasts cultured under hypoxia [8].…”

Treatment of obstructive sleep apnea with continuous positive airway pressure decreases adipocyte fatty acid-binding protein levels

“…This may be explained by the fact that improved oxygenation is a protective factor and decreases A-FABP expression. Similar findings were noted in in vitro studies 20 . This also confirms the conclusion by Lam et al 15 that different intensity of intermittent hypoxia in OSA subjects results in different degrees of heightened expression of A-FABP.…”

Serum adipocyte-fatty acid binding protein level is elevated in severe OSA and correlates with insulin resistance

“…These findings suggests that there may be a threshold effect of OSA on FABP levels and that FABP levels may be upregulated mainly in those subjects with high AHI and a more severe degree of hypoxaemia. There is scanty information regarding the regulation of FABP, although there has been previous evidence of FABP expression being regulated by hypoxia in human trophoblasts in vitro [28]. It is possible that the different intensity of intermittent hypoxia in OSA subjects results in different degrees of heightened expression of A-FABP, which then assumes a mediating role between OSA and metabolic dysfunction.…”