Obesity in Pregnant Women Leads to Lipotoxicity and Dysfunction in Placentas
Introduction: Worldwide, the prevalence of obesity has been steadily increasing over the past few decades. According to the World Health Organization (WHO), obesity worldwide has tripled since 1975. Defined as a Body Mass Index (BMI) of over 30, this condition is a risk factor for many diseases, such as cardiovascular disease and diabetes. In particular, maternal obesity is associated with increased morbidity and mortality for both mother and child. This occurs because the placenta is the interface between the maternal and fetal environments1-2. Researchers have found that maternal obesity causes an increase in cytokines and mediators of the inflammatory signaling pathway leading to chronic inflammation state of the placenta. Possible targets of inflammatory cytokines include proteins involved in lipid metabolism and signaling3. Methods: Three mechanisms were identified that lead to dysfunction of the placenta due to maternal obesity. The first mechanism determined how peroxisomal fatty acid oxidation (FAO) is utilized in comparison to mitochondrial FAO in placentas of obese mothers4. The next mechanism analyzed how the placenta reacts to high levels of circulating insulin from the mother, which crosses the placenta. Specifically, researchers looked at the effects of high circulating insulin on gene expression and regulation5. Lastly, the last mechanism looked at how maternal obesity in general affects gene expression in placental lipid metabolism6. Results: The first mechanism showed that maternal obesity causes a decrease in mitochondrial fatty acid oxidation. This is compensated by an upregulation of peroxisomal fatty acid oxidation, the byproducts of which can cause cellular damage4. The second mechanism showed that obesity and subsequent exposure of the placenta to high levels of insulin leads to insulin insensitivity in the placenta5. The last mechanism showed that pre-gravid obesity significantly modifies the expression of placental genes related to lipid metabolism6. Conclusions: Studies have shown that there is a positive correlation between maternal BMI and placental dysfunction, particularly in regards to lipid metabolism7. Understanding the relationships causing this dysfunction may lead to better targeted and more personalized therapeutic options for long-term effects in the future.
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- Lewis, Rohan M., and Gernot Desoye. “Placental Lipid and Fatty Acid Transfer in Maternal Overnutrition.” Annals of Nutrition and Metabolism, vol. 70, no. 3, 17 Mar. 2017, pp. 228–231., doi:10.1159/000463397.
- Lassance, L., et al., Identification of early transcriptome signatures in placenta exposed to insulin and obesity. Am J Obstet Gynecol, 2015. 212(5): p. 647.e1-11.
- Altmae, S., et al., Maternal Pre-Pregnancy Obesity Is Associated with Altered Placental Transcriptome. PLoS One, 2017. 12(1): p. e0169223.
- Calabuig-Navarro, V., et al., Effect of Maternal Obesity on Placental Lipid Metabolism. Endocrinology, 2017. 158(8): p. 2543-2555.