Poster #096, CHLA LA-HIP
Early-Life High-Fat Diet Alters the Spatial Distribution of CCK-Positive Enteroendocrine Cells in the Developing Mouse Small Intestine
Mentors: Meaghan McCoy, PhD Student and Jason Perez, Graduate Student
Enteroendocrine cells (EECs) regulate gut-brain communication by releasing hormones that influence appetite and feeding behavior. Cholecystokinin (CCK), a satiety hormone produced by EECs, plays an important role in gut-brain signaling. We hypothesize that an early-life high-fat diet (HFD EARLY ) alters the crypt-versus-villus spatial distribution of CCK-positive (CCK+) EECs in the proximal small intestine at postnatal day 21 (P21), which may reshape gut-brain signaling. More than 80% of the US population exceeds the recommended daily limit of calories from saturated fat, contributing to obesity and heart disease. Although EECs regulate appetite and food reward through gut-brain signaling pathways, it remains unclear how HFD EARLY alters cellular architecture that produces these signals during development. Understanding whether HFD EARLY alters spatial distribution of CCK+ EECs may reveal how gut-brain signaling is established and how it contributes to long-term feeding regulation. Control mice were raised on standard chow, while HFD EARLY mice were raised on a high-fat diet during early life; both including both sexes. Proximal small intestine tissue was collected at P21, where CCK+ EECs are concentrated. Immunofluorescent co-staining was performed on tissue sections for CCK and chromogranin A (CHGA), a marker of the total EEC population, allowing CCK+ cells to be quantified as a proportion of all EECs. Using confocal microscopy to identify CCK+/CHGA+ cells and determine their localization within crypt or villus compartments, CCK+ EECs are expected to localize primarily within villi. Preliminary imaging is expected to reveal predominantly crypt-localized CCK+ cells, differing from the expected distribution. We expect HFD EARLY mice to exhibit increased CCK+ EEC localization in crypts and reduced localization in the villi compared with controls, reflecting changes in normal intestinal development. These findings would suggest that HFD EARLY reshapes cellular architecture underlying gut-brain signaling and provide insight into how early nutrition may influence the development of pathways involved in long-term feeding regulation.