Review: Effects of PPAR activation in the placenta and the fetus: Implications in maternal diabetes

Jawerbaum, Alicia; Capobianco, Evangelina

doi:10.1016/j.placenta.2010.12.002

Cited by 70 publications

(64 citation statements)

References 60 publications

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“…Likewise, gene variants may affect survival through childhood or fecundity/fertility in the hypoxic environment. We cannot speculate on the mechanism by which PPARA variants prove advantageous; however, PPAR isoforms are expressed in the placenta (50) and influence female reproductive function (51). It would be of interest to seek association of the PPARA variants with birth weight and measures of placentation in high-altitude natives and Lowlanders exposed to hypoxia.…”

Section: Discussionmentioning

confidence: 99%

Metabolic basis to Sherpa altitude adaptation

Horscroft

Kotwica

Laner

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

165

219

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The Himalayan Sherpas, a human population of Tibetan descent, are highly adapted to life in the hypobaric hypoxia of high altitude. Mechanisms involving enhanced tissue oxygen delivery in comparison to Lowlander populations have been postulated to play a role in such adaptation. Whether differences in tissue oxygen utilization (i.e., metabolic adaptation) underpin this adaptation is not known, however. We sought to address this issue, applying parallel molecular, biochemical, physiological, and genetic approaches to the study of Sherpas and native Lowlanders, studied before and during exposure to hypobaric hypoxia on a gradual ascent to Mount Everest Base Camp (5,300 m). Compared with Lowlanders, Sherpas demonstrated a lower capacity for fatty acid oxidation in skeletal muscle biopsies, along with enhanced efficiency of oxygen utilization, improved muscle energetics, and protection against oxidative stress. This adaptation appeared to be related, in part, to a putatively advantageous allele for the peroxisome proliferator-activated receptor A (PPARA) gene, which was enriched in the Sherpas compared with the Lowlanders. Our findings suggest that metabolic adaptations underpin human evolution to life at high altitude, and could have an impact upon our understanding of human diseases in which hypoxia is a feature. metabolism | altitude | skeletal muscle | hypoxia | mitochondria

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Section: Discussionmentioning

confidence: 99%

Metabolic basis to Sherpa altitude adaptation

Horscroft

Kotwica

Laner

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

165

219

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“…PPARs are ligand-activated nuclear transcription factors which play critical roles in metabolic, developmental, and inflammatory processes. Many PUFAs, including DHA, EPA, AA, and LA, are natural ligands for PPARs (Jawerbaum & Capobianco 2011), and all three PPAR isoforms (a, b/d, and g) are present in the placenta (Hewitt et al 2006a). Knockout studies indicate that PPARg and b/d are particularly important for placental development and vascularization (Jawerbaum & Capobianco 2011).…”

Section: Regulation Of Placental Fatty Acid Transportmentioning

confidence: 99%

“…Many PUFAs, including DHA, EPA, AA, and LA, are natural ligands for PPARs (Jawerbaum & Capobianco 2011), and all three PPAR isoforms (a, b/d, and g) are present in the placenta (Hewitt et al 2006a). Knockout studies indicate that PPARg and b/d are particularly important for placental development and vascularization (Jawerbaum & Capobianco 2011). Once activated, PPARs form heterodimers with retinoic acid X receptor; this complex then binds to the PPAR-response element (PPRE) in the promoter region of target genes to drive their expression.…”

Section: Regulation Of Placental Fatty Acid Transportmentioning

confidence: 99%

Maternal dietary omega-3 fatty acids and placental function

Jones¹,

Mark²,

Waddell³

2014

Reproduction

103

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“…Indeed, we showed that this diet leads to a greater increase in PPARa expression in the hearts of fetuses from diabetic rats. In addition, safflower oil is enriched with linoleic acid, which can activate PPARs by itself and by the production of eicosanoids that can further activate PPARs ( Jawerbaum & Capobianco 2011).…”

Section: Figurementioning

confidence: 99%

“…Fibrates are pharmacological ligands of PPARa used to regulate dyslipidemia, which ameiorate cardiovascular diseases and reduce pro-inflammatory markers in the heart of diabetic patients (Lefebvre et al 2006, Lee et al 2013. The natural ligands of PPARa include leukotriene (LT) B 4 , and certain unsaturated fatty acids such as oleic acid and linoleic acid, which can be efficiently transferred through the placenta (Hihi et al 2002, Herrera et al 2006, Jawerbaum & Capobianco 2011.…”

Section: Introductionmentioning

confidence: 99%

PPAR ligands improve impaired metabolic pathways in fetal hearts of diabetic rats

Kurtz¹,

Capobianco²,

Martínez³

et al. 2014

Journal of Molecular Endocrinology

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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 PPARa 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 PPARa expression in the hearts of male but not female fetuses of diabetic rats when compared with controls. Fetal treatments with the PPARa ligand leukotriene B 4 upregulated the expression of PPARa 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 PPARa 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 PPARa expression, altered lipid metabolism, and increased oxidative and nitridergic pathways were evidenced in hearts of fetuses of diabetic rats and were regulated in a genderdependent manner by treatments enriched with PPAR ligands. Key Words" diabetes in pregnancy " fetus " heart " nitric oxide " PPAR

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Review: Effects of PPAR activation in the placenta and the fetus: Implications in maternal diabetes

Cited by 70 publications

References 60 publications

Metabolic basis to Sherpa altitude adaptation

Metabolic basis to Sherpa altitude adaptation

Maternal dietary omega-3 fatty acids and placental function

PPAR ligands improve impaired metabolic pathways in fetal hearts of diabetic rats

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