Small Intestinal Tuft Cell Activity Associates With Energy Metabolism in Diet-Induced Obesity

Pankaj Arora, Daniel Andersen, Janne Marie Moll, Niels Banhos Danneskiold-Samsøe, Liqin Xu, Biaofeng Zhou, Georgios Kladis, Philipp Rausch, Christopher T. Workman, Karsten Kristiansen, Susanne Brix*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Little is known about the involvement of type 2 immune response-promoting intestinal tuft cells in metabolic regulation. We here examined the temporal changes in small intestinal tuft cell number and activity in response to high-fat diet-induced obesity in mice and investigated the relation to whole-body energy metabolism and the immune phenotype of the small intestine and epididymal white adipose tissue. Intake of high fat diet resulted in a reduction in overall numbers of small intestinal epithelial and tuft cells and reduced expression of the intestinal type 2 tuft cell markers Il25 and Tslp. Amongst >1,700 diet-regulated transcripts in tuft cells, we observed an early association between body mass expansion and increased expression of the gene encoding the serine protease inhibitor neuroserpin. By contrast, tuft cell expression of genes encoding gamma aminobutyric acid (GABA)-receptors was coupled to Tslp and Il25 and reduced body mass gain. Combined, our results point to a possible role for small intestinal tuft cells in energy metabolism via coupled regulation of tuft cell type 2 markers and GABA signaling receptors, while being independent of type 2 immune cell involvement. These results pave the way for further studies into interventions that elicit anti-obesogenic circuits via small intestinal tuft cells.
Original languageEnglish
Article number629391
JournalFrontiers in Immunology
Number of pages13
Publication statusPublished - 2021


  • Tuft cells
  • High fat diet
  • Gut-brain axis
  • GABA
  • Neuroserpin
  • Metabolism
  • Type 2 immune response


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