Abstract

Tuesday 25th November, 16:00 in the Hodgkin Huxley Seminar Room

Talk title: Conversations between mother and fetus: lipid dynamics in pregnancy

Speaker: Marika Charalambous, Professor of Developmental Physiology Department of Medical and Molecular Genetics, King’s College London

Host: Courtney Hanna

Abstract

During a normal pregnancy, maternal metabolism undergoes striking adaptations to meet the nutritional demands of the developing fetus. Anabolic pathways in early pregnancy promote the net accumulation of nutrients within maternal tissues, primarily in the form of triglycerides. A mid-gestation catabolic switch then drives the breakdown of nutrient stores, ensuring the circulating availability of fatty acids and glucose for fetal uptake. These dynamically regulated shifts in maternal nutrient allocation are vital for a healthy pregnancy, as poor adaptations, commonly seen in obese pregnancy, can profoundly disrupt the development and long-term metabolic health of the child.

Fatty acids are crucial components at every stage of fetal development, not just as an energy source, but also to provide building blocks and key signals for organogenesis. Although adipose-derived non-esterified fatty acids can be directly transported across the placenta, the majority are transferred to the maternal liver, a highly adaptive, yet poorly characterised metabolic tissue in pregnancy. Hepatic re-esterification of fatty acids into triglycerides and export into the circulation within lipoproteins underlies the characteristic rise in plasma triglycerides in late gestation and is considered the primary source of fatty acids for the fetus. However, the molecular mechanisms driving this process are not well understood. We recently profiled the liver and plasma lipidomes of virgin and pregnant mice as an unbiased discovery approach for lipid pathways in the maternal liver that are associated with maternal fatty acid provision to the conceptus. With the aid of several genetic models of disrupted lipid metabolism, we have begun to delineate the major maternal lipid pathways that underlie the fatty acid adaptations of late pregnancy. In my talk I will share our current work in the lab which attempts to answer the following questions: How are fatty acids stored and mobilised from maternal tissues? How does the placenta transport these fatty acids to the fetus? Can the fetal-placental unit signal fatty acid demand?