High glucose levels reduce fatty acid oxidation and increase triglyceride accumulation in human placenta

Abstract

25Aim/hypothesis: Placenta of women with gestational diabetes mellitus (GDM) exhibits an 26 altered lipid metabolism. The mechanism by which GDM is linked to alterations in placental lipid 27 metabolism remains obscure. We hypothesized that high-glucose levels reduce mitochondrial fatty 28 acid oxidation (FAO) and increase triglyceride accumulation in human placenta. 29 Methods:To test this hypothesis, we measured FAO, fatty acid esterification, de novo fatty 30 acid synthesis, triglyceride levels and carnitine palmitoyltransferase activities (CPT) in placental 31 explants of women with GDM or with no pregnancy complication. 32 Results:In women with GDM, FAO was reduced by ~30% without change in mitochondrial 33 content, and triglyceride content was 3-fold higher than control group. Likewise, in placental 34

The influence of placental metabolism on fatty acid transfer to the fetus

“…In particular, this should be informed by more detailed experimental analysis of metabolic subcompartments in placental tissue. altered in diabetic pregnancy (40,41). Although the perfused placenta is a highly useful model, it must be remembered that there will be many differences in vivo, including the concentrations of maternal and fetal substrates and hormones, which may both influence placental metabolism and transport.…”

Fatty acid metabolism during maturation affects glucose uptake and is essential to oocyte competence

“…Similarly, obese mice had decreased blastocyst expression of Slc2a1 compared with non-obese mice, suggesting a downregulation of glucose uptake when fatty acid levels are elevated (Bermejo-Alvarez et al 2012). Elevated serum glucose levels in pregnant women correspond to reduced levels of CPT1 activity in placental extracts, thereby decreasing FAO (Visiedo et al 2013). Furthermore, overexpression of glucose transporter Slc2a1 in mouse cardiac tissue increases glucose uptake and oxidation while decreasing FAO, despite a high supply of fatty acids (Yan et al 2009).…”

Review: Placental transport and metabolism of energy substrates in maternal obesity and diabetes

“…154 A recent study reported that placental explants from GDM pregnancies had a two-to 155 three-fold higher glucose uptake and a 50% reduction in fatty acid oxidation [47]. Placentae 156 from normoglycemic pregnancies cultured in high glucose had reduced fatty acid oxidation, 157 along with increased esterification and accumulation of triglycerides [37]. The mechanism 158 proposed was inhibition of carnitine palmitoyltransferase (CPT1) activity by a glucose-159 derived by-product, malonyl-CoA.…”

“…Placental NEFA esterification into triglycerides is thought to be increased in 277 pregnancies complicated by hyperglycemia and/or obesity as a regulatory step to limit fatty 278 acid transfer to the fetus [37]. However, there is no direct evidence to support this notion 279 and earlier studies indicate that de novo fatty acid synthesis is not a significant contributor 280 to triglyceride accumulation in diabetic placentae [84].…”