Nadia obtained her master ICB ! Congrats and welcome to the PhD program!

THE IDENTIFICATION OF LXR-DEPENDENT PATHWAYS IN THE DORSAL ROOT GANGLIA IN MODELS OF OBESITY Peripheral Neuropathy and pain, characterized as injury and dysfunction to the peripheral nervous system, are consequences of obesity. Our laboratory previously showed that chronic inflammation and ER stress pathways induced by nutrient excess and lipid overload, lead to the structural and physiological damage of afferent sensory nerves. We identified that the activation of Liver X Receptors (LXRs), which are lipid- nuclear transcription factors, protect the cell from the lipid-induced ER stress and from neuropathic pain in obesity. Their molecular role in the peripheral nervous system remains to be fully elucidated; they are of particular interest due to their pivotal roles in the regulation of lipid homeostasis, membrane phospholipids, and inflammation identified in metabolic tissues such as the liver. The dorsal root ganglia (DRG) contains afferent sensory neuron cell bodies and carries sensory messages to the central nervous system from peripheral nerves. Here, we confirmed the

expression of LXRs in the DRG and provided potential mechanisms underlying the improvement of pain after LXR activation in obese rodents. We characterized lipid homeostasis of neurons activated by LXR in presence of fat and observed that LXR may regulate multiple lipid pathways involving ceramide and arachidonic acid. To this end, we performed ex vivo studies to determine the consequences of LXR activation on key lipid enzymes. Our data shows that, in the DRG, LXR activation may decrease prostaglandin synthesis and modify membrane lipids that may be involved in the attenuation of obesity-induced pain and neuropathy.

THESIS COMMITTEE

Virginie Mansuy-Aubert, Ph.D. Professor and Mentor Department of
Loyola University Chicago Health Science Division

Jordan Beach, Ph.D. Assistant Professor Department of Loyola University Chicago Health Science Division

Edward Campbell, Ph.D. Assistant Professor Department of Loyola University Chicago Health Science Division