Hyman J. Zimmerman Hepatotoxicity SOA: Lipotoxicity in the Liver

Description

Organs and tissues exhibit distinct features of structural organization at various scales to meet functional demands and adapt to challenges to maintain homeostasis and viability. However, detailed resolution of native intracellular molecular architecture and the relationship of molecular architectural formations to metabolic function remains poorly understood. This lecture features presentation of subcellular architecture at the nanoscale level in native liver tissue and reviews how these structures are regulated during both physiological responses and metabolic disease. Such nanoscale resolution observations are made possible by utilizing multiple imaging platforms, including enhanced focused ion beam scanning electron microscopy (FIB-SEM), followed by deep-learning–based image segmentation, combined with biochemical and physiological approaches. This line of inquiry demonstrates that hepatic subcellular molecular architecture is highly dynamic and regulated, integrated with the metabolic program of the cell, and critical for adaptive homeostasis in health and its disruption in disease.