Sathish Kumar Natarajan
- Associate Professor & Graduate Chair, Department of Nutrition & Health Sciences
snatarajan2@unl.edu
402-805-7520
The long-term goal of my research program is to develop a nutraceutical approach to mitigate liver and placental lipotoxicity that occurs during acute fatty liver of pregnancy and maternal obesity, respectively. Trophoblasts are specialized cells in the placenta that facilitate nutrient transport to the developing fetus. We have identified dietary palmitoleate, an omega-7 mono unsaturated fatty acids is protective against placental lipoapoptosis caused due to the exposure of lipotoxic fatty acids that are elevated in acute fatty liver of pregnancy and maternal obesity. Further, we are also interested in elucidating the role of placental trophoblast infection with Zika virus and the protective role of dietary-palmitoleate supplementation in preventing against Zika virus-induced placental trophoblast apoptosis. Identifying palmitoleate as a cytoprotective nutrient will result in potential nutrient therapy for the prevention of devastating consequences of fetal organ infection with Zika virus.
Placental Trophoblast Lipotoxicity during Maternal Obesity
Obesity during pregnancy increases the risk for maternal complications such as gestational diabetes, preeclampsia, and maternal inflammation. Maternal obesity also increases the risk of childhood obesity, fetal intrauterine growth restriction (IUGR) and diabetes in childhood. Placental trophoblast apoptosis is documented in patients with preeclampsia and IUGR due to hypoxia. Increased circulating free fatty acids (FFA) in obesity due to adipose lipolysis induces lipoapoptosis to hepatocytes, cholangiocytes, and pancreatic-β-cells. I initiated studies to test the lipotoxic role of saturated free fatty acids in placental trophoblast during maternal obesity. Our published work shows that saturated FFAs induce placental trophoblast lipoapoptosis (PLoSOne 2021). We also observed that saturated FFAs caused a concentration-dependent increase in placental trophoblast lipoapoptosis. Further, addition of saturated FFAs to placental trophoblasts led to increased levels of cleaved-PARP and cleaved caspase 3 in these trophoblasts. Co-treatment of palmitate with lipopolysaccharide to placental trophoblasts exacerbates palmitate-induced placental trophoblast lipoapoptosis suggesting that maternal inflammation aggravates FFA-induced lipoapoptosis. Interestingly, palmitoleate treatment protects against palmitate-induced placental trophoblast lipoapoptosis. The protection offered by palmitoleate support the therapeutic potential of palmitoleate against FFA-induced placental lipotoxicity in maternal obesity.
Featured Publications
Sahoo PK, Krishnamoorthy C, Wood JR, Hanson C, Anderson-Berry A, Mott JL, Natarajan SK. Cell Death Dis. 2024 Jan 11;15(1):31. doi: 10.1038/s41419-023-06415-6. PMID: 38212315
Muthuraj PG, Krishnamoorthy C, Anderson-Berry A, Hanson C, Natarajan SK. Nutrients. 2022 Dec 27;15(1):124. doi: 10.3390/nu15010124. PMID: 36615782
Natarajan SK, Bruett T, Muthuraj PG, Sahoo PK, Power J, Mott JL, Hanson C, Anderson-Berry A. PLoS One. 2021 Apr 22;16(4):e0249907. doi: 10.1371/journal.pone.0249907. eCollection 2021. PMID: 33886600
Natarajan SK, Stringham BA, Mohr AM, Wehrkamp CJ, Lu S, Phillippi MA, Harrison-Findik D, Mott JL. J Lipid Res. 2017 May;58(5):866-875. doi: 10.1194/jlr.M071357. Epub 2017 Mar 1. PMID: 28250026
Natarajan SK, Ingham SA, Mohr AM, Wehrkamp CJ, Ray A, Roy S, Cazanave SC, Phillippi MA, Mott JL. Hepatology. 2014 Dec;60(6):1942-56. doi: 10.1002/hep.27175. Epub 2014 Jun 20. PMID: 24753158