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ER Structure and Function in Metabolic Regulation
Ana Paula Arruda
Department of Nutritional Sciences and Toxicology, University of California Berkeley.
The liver is a hub of metabolism which sharply adapts to fluctuations in nutrient availability to maintain tissue and systemic homeostasis. Although hepatocytes within the liver are morphologically similar, these cells present distinct metabolic functional capacity depending on their spatial location in the liver lobe, a process called zonation. By using enhanced FIB-SEM combined with deep-learning based segmentation, we resolved the fine details of subcellular organization in liver cells in different nutritional states across the liver lobe. We found that in lean healthy mice, hepatic ER undergoes significant structural re-organization in fasting, and this remodeling is impaired in obese conditions. We also detected that the response to fasting is zonated towards the mid-lobular and periportal hepatocytes but not present in pericentral hepatocytes. These findings show that hepatic ER’s architecture is dynamic, responds to changes in nutritional states and is critical for metabolic homeostasis and tissue health.