Obesity alters adrenergic and chemosensory signaling pathways that regulate ghrelin secretion in the human gut

Autor: Emilio Canovai, Kathrin I. Liszt, Qiaoling Wang, Theo Thijs, Eveline Deloose, Matthias Lannoo, Jan Tack, Laurens J. Ceulemans, Inge Depoortere, Ricard Farré
Rok vydání: 2019
Předmět:
nutrient sensing
Male
0301 basic medicine
medicine.medical_specialty
Fluorescent Antibody Technique
Nutrient sensing
Real-Time Polymerase Chain Reaction
Biochemistry
Receptors
G-Protein-Coupled
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
stomatognathic system
Taste receptor
Internal medicine
Intestine
Small
Genetics
medicine
Humans
Secretion
Obesity
RNA
Messenger
bitter taste receptor
Molecular Biology
sympathetic nervous system
Mucous Membrane
Chemistry
digestive
oral
and skin physiology
Denatonium
glucose sensors
Middle Aged
Ghrelin
Glucose
030104 developmental biology
Endocrinology
TAS2R10
Female
Signal transduction
hormones
hormone substitutes
and hormone antagonists
030217 neurology & neurosurgery
Ghrelin secretion
Signal Transduction
Biotechnology
Zdroj: The FASEB Journal. 33:4907-4920
ISSN: 1530-6860
0892-6638
Popis: 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. ispartof: FASEB JOURNAL vol:33 issue:4 pages:4907-4920 ispartof: location:United States status: published
Databáze: OpenAIRE
Externí odkaz: