These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: High glucose levels reduce fatty acid oxidation and increase triglyceride accumulation in human placenta.
    Author: Visiedo F, Bugatto F, Sánchez V, Cózar-Castellano I, Bartha JL, Perdomo G.
    Journal: Am J Physiol Endocrinol Metab; 2013 Jul 15; 305(2):E205-12. PubMed ID: 23673156.
    Abstract:
    Placentas of women with gestational diabetes mellitus (GDM) exhibit an altered lipid metabolism. The mechanism by which GDM is linked to alterations in placental lipid metabolism remains obscure. We hypothesized that high glucose levels reduce mitochondrial fatty acid oxidation (FAO) and increase triglyceride accumulation in human placenta. To test this hypothesis, we measured FAO, fatty acid esterification, de novo fatty acid synthesis, triglyceride levels, and carnitine palmitoyltransferase activities (CPT) in placental explants of women with GDM or no pregnancy complication. In women with GDM, FAO was reduced by ~30% without change in mitochondrial content, and triglyceride content was threefold higher than in the control group. Likewise, in placental explants of women with no complications, high glucose levels reduced FAO by ~20%, and esterification increased linearly with increasing fatty acid concentrations. However, de novo fatty acid synthesis remained unchanged between high and low glucose levels. In addition, high glucose levels increased triglyceride content approximately twofold compared with low glucose levels. Furthermore, etomoxir-mediated inhibition of FAO enhanced esterification capacity by ~40% and elevated triglyceride content 1.5-fold in placental explants of women, with no complications. Finally, high glucose levels reduced CPT I activity by ~70% and phosphorylation levels of acetyl-CoA carboxylase by ~25% in placental explants of women, with no complications. We reveal an unrecognized regulatory mechanism on placental fatty acid metabolism by which high glucose levels reduce mitochondrial FAO through inhibition of CPT I, shifting flux of fatty acids away from oxidation toward the esterification pathway, leading to accumulation of placental triglycerides.
    [Abstract] [Full Text] [Related] [New Search]