title: PPAR ligands improve impaired metabolic pathways in fetal hearts of diabetic rats.
abstract: In maternal diabetes, the fetal heart can be structurally and functionally affected. Maternal diets enriched in certain unsaturated fatty acids can activate the nuclear receptors peroxisome proliferator-activated receptors (PPARs) and regulate metabolic and anti-inflammatory pathways during development. Our aim was to investigate whether PPARα expression, lipid metabolism, lipoperoxidation, and nitric oxide (NO) production are altered in the fetal hearts of diabetic rats, and to analyze the putative effects of in vivo PPAR activation on these parameters. We found decreased PPARα expression in the hearts of male but not female fetuses of diabetic rats when compared with controls. Fetal treatments with the PPARα ligand leukotriene B4 upregulated the expression of PPARα and target genes involved in fatty acid oxidation in the fetal hearts. Increased concentrations of triglycerides, cholesterol, and phospholipids were found in the hearts of fetuses of diabetic rats. Maternal treatments with diets supplemented with 6% olive oil or 6% safflower oil, enriched in unsaturated fatty acids that can activate PPARs, led to few changes in lipid concentrations, but up-regulated PPARα expression in fetal hearts. NO production, which was increased in the hearts of male and female fetuses in the diabetic group, and lipoperoxidation, which was increased in the hearts of male fetuses in the diabetic group, was reduced by the maternal treatments supplemented with safflower oil. In conclusion, impaired PPARα expression, altered lipid metabolism, and increased oxidative and nitridergic pathways were evidenced in hearts of fetuses of diabetic rats and were regulated in a gender-dependent manner by treatments enriched with PPAR ligands.
authors.affiliation: Laboratory of Reproduction and Metabolism CEFyBO-CONICET, School of Medicine, University of Buenos Aires, Paraguay 2155, 17th Floor, 1121 Buenos Aires, Argentina Department of Pathology Schullich School of Medicine and Dentistry, Lawson Health Research Institute, St Joseph's Health Care, University of Western Ontario, London, Ontario, Canada.
authors.forename: Melisa
authors.initials: M
authors.lastname: Kurtz
authors.affiliation: Laboratory of Reproduction and Metabolism CEFyBO-CONICET, School of Medicine, University of Buenos Aires, Paraguay 2155, 17th Floor, 1121 Buenos Aires, Argentina Department of Pathology Schullich School of Medicine and Dentistry, Lawson Health Research Institute, St Joseph's Health Care, University of Western Ontario, London, Ontario, Canada.
authors.forename: Evangelina
authors.initials: E
authors.lastname: Capobianco
authors.affiliation: Laboratory of Reproduction and Metabolism CEFyBO-CONICET, School of Medicine, University of Buenos Aires, Paraguay 2155, 17th Floor, 1121 Buenos Aires, Argentina Department of Pathology Schullich School of Medicine and Dentistry, Lawson Health Research Institute, St Joseph's Health Care, University of Western Ontario, London, Ontario, Canada.
authors.forename: Nora
authors.initials: N
authors.lastname: Martinez
authors.affiliation: Laboratory of Reproduction and Metabolism CEFyBO-CONICET, School of Medicine, University of Buenos Aires, Paraguay 2155, 17th Floor, 1121 Buenos Aires, Argentina Department of Pathology Schullich School of Medicine and Dentistry, Lawson Health Research Institute, St Joseph's Health Care, University of Western Ontario, London, Ontario, Canada.
authors.forename: Sabrina Lorena
authors.initials: SL
authors.lastname: Roberti
authors.affiliation: Laboratory of Reproduction and Metabolism CEFyBO-CONICET, School of Medicine, University of Buenos Aires, Paraguay 2155, 17th Floor, 1121 Buenos Aires, Argentina Department of Pathology Schullich School of Medicine and Dentistry, Lawson Health Research Institute, St Joseph's Health Care, University of Western Ontario, London, Ontario, Canada.
authors.forename: Edith
authors.initials: E
authors.lastname: Arany
authors.affiliation: Laboratory of Reproduction and Metabolism CEFyBO-CONICET, School of Medicine, University of Buenos Aires, Paraguay 2155, 17th Floor, 1121 Buenos Aires, Argentina Department of Pathology Schullich School of Medicine and Dentistry, Lawson Health Research Institute, St Joseph's Health Care, University of Western Ontario, London, Ontario, Canada a.jawerbaum@gmail.com.
authors.forename: Alicia
authors.initials: A
authors.lastname: Jawerbaum
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004032:Diet; D005260:Female; D005318:Fetal Heart / Q000378:metabolism*; D008024:Ligands; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D008297:Male; D053858:Metabolic Networks and Pathways; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D000069463:Olive Oil; D010084:Oxidation-Reduction; D047493:PPAR alpha / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D010938:Plant Oils / Q000008:administration & dosage; D011247:Pregnancy; D051381:Rats; D012450:Safflower Oil / Q000008:administration & dosage
chemical_list: D008024:Ligands; D000069463:Olive Oil; D047493:PPAR alpha; D047492:Peroxisome Proliferator-Activated Receptors; D010938:Plant Oils; D009569:Nitric Oxide; D012450:Safflower Oil
keywords: PPAR; diabetes in pregnancy; fetus; heart; nitric oxide