Dietary lipids modulate Notch signaling and influence adult intestinal development and metabolism in Drosophila

摘要: Tissue homeostasis is a complex balance of developmental signals and environmental cues that dictate stem cell function. However, it remains poorly understood how nutrients interface with pathways. Using the Drosophila midgut as model we found during first four days adult life, dietary lipids including cholesterol, determine many enteroendocrine (ee) cells differentiate persist in posterior where are preferentially absorbed. The nuclear hormone receptor Hr96 which functions to control sterol trafficking, storage, utilization, required for sterol-mediated changes ee number. Dietary cholesterol influences new intestinal epithelial differentiation from by altering level persistance Notch signaling. Exogenous modulate signaling changing stability Delta ligand intracellular domain their trafficking endosomal vesicles. Lipid-modulated occurs other nutrient-dependent tissues such ovary, suggesting sensitive cellular levels. These diet-mediated alterations number young animals contribute metabolic program adapted prevailing nutrient environment persists after diet changes. A low also slows proliferation tumors initiated disruptions pathway. studies show specific can modify key intercellular pathway shift cause lasting tissue structure physiology.