Sathish Kumar NatarajanAssistant Professor
Ph.D., Biomedical Sciences, Dr. MGR Medical University, Tamilnadu, India, 2008
M.S., Biochemistry, University of Madras, Tamilnadu, India, 2001
B.S., Biochemistry, University of Madras, Tamilnadu, India, 1999
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.
Acute Fatty Liver of Pregnancy
Dr. Natarajan's lab is focused on understanding the molecular mechanism of 3-hydroxy fatty acid-induced lipotoxicity to the placenta and liver during acute fatty liver of pregnancy (AFLP), a catastrophic maternal liver disease. AFLP is an obstetric and medical emergency that develops in the last trimester of pregnancy. Fetuses with a mutation in the mitochondrial long-chain hydroxy acyl-CoA dehydrogenase (LCHAD) is highly associated with the mother developing AFLP. Placenta (an organ that helps the fetus growth) with the LCHAD mutation results in the accumulation of toxic lipid intermediates, like 3‑hydroxy fatty acids. These accumulated toxic lipid metabolites from the placenta enter into maternal circulation and damages maternal liver resulting in maternal liver injury observed in patients with AFLP.
Dr. Natarajan's lab works in identifying novel therapeutic nutrient molecule that could mitigate placenta and liver injury in patients with AFLP. We have identified that palmitoleate, a mono-unsaturated omega-7 fatty acid protects against placental trophoblast and hepatocyte lipoapoptosis and can be used as a potential therapeutic nutrient molecule to treat patients with AFLP. The information obtained from the mechanism of liver injury from our studies will help in advancing and broadening the general knowledge of the liver injury and steatosis in fatty liver disease. Further, the protective role of palmitoleate will also be useful in treating patients with non-alcoholic fatty liver disease (NAFLD).
Zika Virus-induced Apoptosis
Zika Virus infection during pregnancy results in the development of Congenital Zika Syndrome, which includes the development of microcephaly, ocular abnormalities, and intrauterine growth retardation. Zika Virus infects placenta and results in the vertical transmission of the virus to the fetal brain. Further, Infection of Zika Virus induces apoptosis to placental trophoblast, neuronal progenitors, and testicular cells. Dr. Natarajan's lab has identified a nutrient compound that protects against Zika Virus-induced placental trophoblast and neuronal cell apoptosis.
Placental Trophoblast Lipotoxicity during Maternal Obesity
Obesity during pregnancy increases the risk for maternal complications like gestational diabetes, preeclampsia, and maternal inflammation. Maternal obesity also increases the risk of childhood obesity, fetal intrauterine growth restriction (IUGR) and diabetes to the children. 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. During the third trimester of pregnancy, there is an increase in maternal lipolysis and release of FFA into the circulation. Dr. Natarajan's lab long-term goal is to identify a nutrient compound that would mitigate the placental injury and dysfunction caused due to the increased circulating FFA during maternal obesity.
Areas of Expertise:
• Studied pathways of liver lipotoxicity in non-alcoholic fatty liver disease (NAFLD)
• Established that proline and pipecolate metabolism promote cell survival
• Determined the mechanisms by which dysfunction in placental metabolism affects maternal liver health.
• Demonstrated that liver cirrhosis results in intestinal and renal dysfunction