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Obesity alters adrenergic and chemosensory signaling pathways that regulate ghrelin secretion in the human gut
Author(s) -
Wang Qiaoling,
Liszt Kathrin I.,
Deloose Eveline,
Canovai Emilio,
Thijs Theo,
Farré Ricard,
Ceulemans Laurens J.,
Lannoo Matthias,
Tack Jan,
Depoortere Inge
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201801661rr
Subject(s) - ghrelin , endocrinology , medicine , secretion , receptor , enteroendocrine cell , signal transduction , agonist , taste , biology , chemistry , microbiology and biotechnology , hormone , endocrine system , biochemistry
Chemosensory signaling in organs such as the mouth and gut contributes to the mechanisms that control metabolism. We investigated the chemosensory pathways that regulate secretion of the hunger hormone ghrelin in response to neurotransmitters, bitter and sweet tastants at the cellular level in the human gut mucosa, and the disturbances in this regulatory pathway induced by obesity. Obesity impaired ghrelin protein production and adrenalin‐induced ghrelin secretion in fundic cells, which was counterbalanced by somatostatin. Bitter agonists selective for taste receptor type 2 (TAS2Rs), TAS2R5 and TAS2R10 stimulated ghrelin secretion in fundic cells. The stimulatory effect of the broadly tuned bitter agonist, denatonium benzoate, was selectively blunted by obesity in the small intestine but not in the fundus. Luminal glucose concentrations inhibited ghrelin secretion via sodium‐dependent glucose cotransporter and taste receptor type 1 member 3. Obesity altered the sensitivity of the ghrelin cell to glucose in the small intestine but not in the fundus. Sweet taste receptor activation inhibited bitter taste signaling of the ghrelin cell. In conclusion, obesity impairs the sympathetic drive that controls ghrelin release in the fundus and affects the sensitivity of the ghrelin cell to bitter and sweet stimuli in the small intestine but not in the fundus. Region‐selective targeting of gut taste receptors in obesity is indicated.—Wang, Q., Liszt, K. I., Deloose, E., Canovai, E., Thijs, T., Farré, R., Ceulemans, L. J., Lannoo, M., Tack, J., Depoortere, I. Obesity alters adrenergic and chemosensory signaling pathways that regulate ghrelin secretion in the human gut. FASEB J. 33, 4907–4920 (2019). www.fasebj.org