Small Intestinal Tuft Cell Activity Associates With Energy Metabolism in Diet-Induced Obesity
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Small Intestinal Tuft Cell Activity Associates With Energy Metabolism in Diet-Induced Obesity. / Arora, Pankaj; Andersen, Daniel; Moll, Janne Marie; Danneskiold-Samsøe, Niels Banhos; Xu, Liqin; Zhou, Biaofeng; Kladis, Georgios; Rausch, Philipp; Workman, Christopher T.; Kristiansen, Karsten; Brix, Susanne.
In: Frontiers in Immunology, Vol. 12, 629391, 2021.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - Small Intestinal Tuft Cell Activity Associates With Energy Metabolism in Diet-Induced Obesity
AU - Arora, Pankaj
AU - Andersen, Daniel
AU - Moll, Janne Marie
AU - Danneskiold-Samsøe, Niels Banhos
AU - Xu, Liqin
AU - Zhou, Biaofeng
AU - Kladis, Georgios
AU - Rausch, Philipp
AU - Workman, Christopher T.
AU - Kristiansen, Karsten
AU - Brix, Susanne
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - GABA
KW - gut-brain axis
KW - high fat diet
KW - metabolism
KW - neuroserpin
KW - tuft cells
KW - type 2 immune responses
U2 - 10.3389/fimmu.2021.629391
DO - 10.3389/fimmu.2021.629391
M3 - Journal article
C2 - 34122403
AN - SCOPUS:85107664963
VL - 12
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
M1 - 629391
ER -
ID: 272644199