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Diet-induced changes in tuft cell dynamics couple with type 2 immune response modulation and energy metabolism

ABSTRACT: Purpose: To examine the temporal changes in intestinal tuft cell number and activity in response to intake of a high fat diet and investigate the relation to whole-body energy metabolism and the immune phenotype of the small intestine and epididymal white adipose tissue (eWAT). Methods: C57BL/6J mice were fed either a low fat reference diet (RFD, 10 % kcal fat) or a high fat diet (HFD, 60% kcal fat) for 9 or 22 weeks, followed by characterization of whole-body metabolic parameters, transcription profiles of sorted intestinal tuft cells, and immune phenotypes of tissues. Results: HFD feeding was associated with reductions in the overall number of small intestinal epithelial cells and tuft cells and reduced expression of the intestinal type 2 tuft cell markers Il25 and Tslp. Amongst >1,700 diet-regulated genes in tuft cells identified by RNA-seq, we observed an early association between body mass expansion and increased expression of Serpini1, which encodes the serine protease inhibitor neuroserpin. By contrast, tuft cell expression of genes encoding the GABA-receptors linked to reduced body mass gain. Although we observed a HFD-induced change in the eWAT inflammatory profile, the small intestinal lamina propria displayed a consistent non-inflammatory phenotype, and small intestinal tuft cell-derived transcripts were found to correlate with whole body metabolic features independently of intestinal immune cell involvement. Conclusion: Our These findings point to a role for small intestinal tuft cells in systems-wide metabolic regulation.

ORGANISM(S): Mus musculus

PROVIDER: GSE141002 | GEO | 2019/11/26

REPOSITORIES: GEO

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Project description:Objective: Procyanidins are polyphenolic bioactive compounds that exert beneficial effects against obesity and its related diseases. The aim of this study was to evaluate whether the supplementation with low doses of a grape seed procyanidin extract (GSPE) to dams during pre and postnatal periods has biological effects on their offspring at youth. Design: The metabolic imprinting effect of GSPE was evaluated in 30 days-old male offspring of four groups of rats that were fed either a standard diet (STD) or a high-fat diet (HFD) and supplemented with either GSPE at 25 mg per kg of body weight/day or vehicle during pregnancy and lactation. Results: A significant increase in the adiposity index and in the weight of all the white adipose tissue depots studied (retroperitoneal â??RWAT-, mesenteric â??MWAT-, epididymal â??EWAT- and inguinal â??IWAT-) was observed in offspring of dams fed with a HFD and treated with GSPE (HFT group), compared to the offspring of dams fed with the same diet and that do not received procyanidins (HF group). HFT animals also showed a higher number of cells in the EWAT, a sharply decrease of the circulating levels of monocyte chemoattractant protein-1 (MCP-1) as well as a moderate, but significant, decrease of plasma glycerol levels. The transcriptomic analysis performed in the EWAT showed 238 genes differentially expressed between HF and HFT animals, covering an entire range of processes related with the immune function and the inflammatory response (the metabolic pathway mainly reflected in the EWAT), adipose tissue remodeling and function, lipid and glucose homeostasis and metabolism of methyl groups. Conclusion: GSPE treatment to dams fed a HFD during pregnancy and lactation increases adiposity, decreases the circulating levels of MCP-1 and modulates the expression of key genes involved in the adipose tissue metabolism of their offspring. The microarray study was performed with the EWAT RNA samples of rats from the HF and the HFT groups (n=8 animals each).

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Diet-induced changes in tuft cell dynamics couple with type 2 immune response modulation and energy metabolism

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