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High glucose levels reduce fatty acid oxidation and increase triglyceride accumulation in human placenta
- Source :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Publication Year :
- 2013
- Publisher :
- American Physiological Society, 2013.
-
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. © 2013 the American Physiological Society.<br />This study was supported by a grant from the Carlos III Health Institute (CP08/00106), the Spanish Ministry of Science and Innovation (SAF2009-11282), and the FP7-PEOPLE-2009-RG (PIRG06-GA-2009-25369) to G. Perdomo; a grant from the Consejería de Salud, Junta de Andalucía (N°0269/05.2005) to J. L. Bartha; and grant from the Carlos III Health Institute (PI11/00676) to F. Bugatto.
- Subjects :
- Adult
Blood Glucose
medicine.medical_specialty
Physiology
Placenta
Endocrinology, Diabetes and Metabolism
Blotting, Western
Citrate (si)-Synthase
Biology
chemistry.chemical_compound
Organ Culture Techniques
Carnitine palmitoyltransferase 1
Pregnancy
Physiology (medical)
Internal medicine
medicine
Humans
Hypoglycemic Agents
Beta oxidation
Triglycerides
Glycated Hemoglobin
Anthropometry
Carnitine O-Palmitoyltransferase
Triglyceride
Fatty acid metabolism
Fatty Acids
Lipid metabolism
medicine.disease
Mitochondria
Gestational diabetes
Diabetes, Gestational
Cholesterol
medicine.anatomical_structure
Endocrinology
chemistry
Epoxy Compounds
Female
Carnitine palmitoyltransferase I
Oxidation-Reduction
Subjects
Details
- ISSN :
- 15221555 and 01931849
- Volume :
- 305
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Endocrinology and Metabolism
- Accession number :
- edsair.doi.dedup.....459a01c99690ac66adc026d5cf61e0ef