Seminars - NEWS & EVENTS - Department of Life Science

[Regular Seminars] 2024학년도 1학기 생명과학과 6차 세미나

-Speaker : 정원일 교수 (KAIST 의과학대학원)
-Topic : Pathways beyond Metabolism in the Liver
-Date : 2024.05.20 (월) 10:30 ~
-Location : 시대융합관-B121호

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Recently, in contrast to viral hepatitis, alcoholic-related and non-alcoholic fatty liver diseases have rapidly increased worldwide. Unfortunately, no therapeutic medication exists against both types of liver diseases besides abstinence and exercise. In order to develop new therapeutics, the current theoretical approach towards liver disease should change. Despite new technologies such as single cell RNA-sequencing and spatial transcriptomics, current approach based on oxygen and nutrient gradients in the liver fails to explain various zonation-dependent functions of hepatocytes and non-parenchymal cells. While some papers have suggested innervating CNS signaling to regulate diverse hepatic functions, liver transplant studies have demonstrated normal hepatic functions in the recipients without any post-transplant innervation. Such contradiction elicits unexplored sources of neurotransmitters and neurological signaling pathways in our liver. Here, we propose a novel paradigm of glutamatergic signaling in the liver. Under normal conditions, hepatocytes generate and secrete glutamate through multiple ways for survival, protection against fibrosis, and interaction with neighboring cells. Glutamate signaling is mainly initiated by the binding of the released glutamate to metabotropic glutamate receptor 5 (mGluR5) in non-parenchymal cells (NPCs) such as hepatic stellate cells, natural killer cells, and Kupffer cells. Under stressful conditions such as chronic alcohol consumption, the mGluR5 activation is greatly enhanced. Therefore, we investigate that synthesis and release of glutamate through multiple cascade signaling pathways serve as important pathophysiological regulator of liver disease progression by regulating both metabolism and immune responses. We posit that these newly identified glutamatergic hepatocytes may broaden our understanding of hepatic neurologic pathways, specifically in maintaining hepatic metabolism and immune homeostasis and attenuating liver diseases.

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