Prior High Fiber Intake Impinges on the Cellular Responses of Mesenteric Adipose and Intestinal Tissues to Subsequent High Fat Feeding
Dietary modification by consuming plant-based food with high fiber content is a primary strategy to induce weight loss in obese individuals. However, long-term usage of such fiber-enriched dieting is challenging and rapid weight regain often occurs once the high-fat dietary habit resumes. Currently, how do adipose and intestinal tissues respond to a switch between high-fiber and high-fat diet remains unknown. Here, we applied C57BL/6J mice to chow diet (CD)/high-fiber diet (HfiD)-to-high-fat diet (HFD) switching paradigms and collected mesenteric white adipose tissue (mWAT), duodenum and colon tissue sections at different time points for single-nucleus profiling and spatially resolved transcriptomic analysis, respectively. We show that the progenitors and adipocytes of HfiD-fed mWAT are more sensitive to HFD-induced molecular changes. In addition, HfiD feeding prevents the subsequent HFD-induced expansion of immune-related enterocytes in duodenum and reverses the HFD-induced enterocyte-to-goblet cell conversion in colon. Moreover, HfiD-induced microbiome changes are mostly abrogated upon HFD feeding. Our results indicate that prior HfiD feeding can alter the cellular response of adipose and intestinal tissues to subsequent HFD feeding, which highlights the impact of dietary interventions with fiber-rich food for obesity treatment from a different perspective. Our data provide a spatiotemporal resource for future hypothesis-driven studies on the mechanisms of adipose and intestinal tissue plasticity in response to diet switches. Overall design: To investigate how switch between HfiD and HFD shapes the intestinal and adipose tissues, we applied freshly weaned C57BL/6J male mice to either a control diet (CD) (AIN93G) or an HfiD (AIN93G supplemented with inulin for 5 weeks, before switching both groups to an HFD (AIN93G supplemented with 60 kcal% fat) and collected different cohorts of mice right before, 4 and 8 weeks after switching to HFD for analysis.