Figure 10. Proposed model for microbiota-dependent HF feeding-induced EEC silencing.

At early postprandial stages after consumption of a high fat (HF) meal, dietary triglyceride (TG) is hydrolyzed to monoglycerides and free fatty acids (FA) by lipases in the gut lumen. FA are taken up by enterocytes and re-esterified into TG which is packaged into chylomicrons (CM) for basolateral secretion. FA and dietary glucose stimulate EECs, increasing [Ca²⁺]_i and inducing secretion of hormones like CCK, PYY and GLP-1. During and after HF feeding, FA taken up by enterocytes are stored in cytosolic lipid droplets (LD) in addition to secreted CM. Moving into later postprandial stages, HF feeding and presence of gut microbiota lead to ER stress in EECs. HF feeding also promotes overgrowth of the gut bacterial community including enrichment of Acinetobacter sp. Activation of ER stress pathways by these nutritional and microbial stimuli cause EECs to retract their apical processes and reduce their nutrient sensitivity at the late postprandial stage, a process we call ‘EEC silencing’.