Obesity Impairs Oligopeptide/Amino Acid‐Induced Ghrelin Release and Smooth Muscle Contractions in the Human Proximal Stomach

Vancleef, Laurien; Thijs, Theo; Baert, Florence; Ceulemans, Laurens J.; Canovai, Emilio; Wang, Qiaoling; Steensels, Sandra; Segers, Anneleen; Farré, Ricard; Pirenne, Jacques; Lannoo, Matthias; Tack, Jan; Depoortere, Inge

doi:10.1002/mnfr.201700804

Cited by 17 publications

(35 citation statements)

References 49 publications

(84 reference statements)

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“…The entire stomach and part of the small intestine (duodenum and jejunum) were collected from circulatory death or brain death organ donors (lean). Detailed protocols for tissue preparations from organ donors have been previously published (17). A large part of the stomach and a segment of the jejunum were obtained from obese nondiabetic patients who underwent sleeve gastrectomy or Roux‐en‐Y gastric bypass surgery, respectively.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2019

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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). http://www.fasebj.org

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Section: Methodsmentioning

confidence: 99%

“…The rise in plasma ghrelin levels before each meal is mediated by the sympathetic nervous system and involves β 1 ‐adrenergic receptors (AR) on the ghrelin cell in mice (13–15). The magnitude of the postprandial decline is determined by the macronutrient composition of the meal and is partially regulated by taste receptors (16, 17).…”

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

et al. 2019

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“…[63][64][65][66][67] In particular, the expression of αgustducin and α-transducin (both comprising G protein α-subunits detected in the gustatory system 68 ) in octanoyl ghrelin-producing cells indicates an important role in nutrient sensing processes. [63][64][65][66][67] In particular, the expression of αgustducin and α-transducin (both comprising G protein α-subunits detected in the gustatory system 68 ) in octanoyl ghrelin-producing cells indicates an important role in nutrient sensing processes.…”

Section: Stomachmentioning

confidence: 99%

A role for taste receptors in (neuro)endocrinology?

Behrens

Meyerhof

2019

J Neuroendocrinology

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The sense of taste is positioned at the forefront when it comes to the interaction of our body with foodborne chemicals. However, the role of our taste system, and in particular its associated taste receptors, is not limited to driving food preferences leading to ingestion or rejection before other organs take over responsibility for nutrient digestion, absorption and metabolic regulation. Taste sensory elements do much more. On the one hand, extra‐oral taste receptors from the brain to the gut continue to sense nutrients and noxious substances after ingestion and, on the other hand, the nutritional state feeds back on the taste system. This intricate regulatory network is orchestrated by endocrine factors that are secreted in response to taste receptor signalling and, in turn regulate the taste receptor cells themselves. The present review summarises current knowledge on the endocrine regulation of the taste perceptual system and the release of hunger/satiety regulating factors by gastrointestinal taste receptors. Furthermore, the regulation of blood glucose levels via the activation of pancreatic sweet taste receptors and subsequent insulin secretion, as well as the influence of bitter compounds on thyroid hormone release, is addressed. Finally, the central effects of tastants are discussed briefly.

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“…In contrast, bitter substances activate 25 subtypes of the taste receptor type 2 (T2Rs) family. 16 Interestingly, the T1R3 subunit was expressed in mouse but not human fundic smooth muscle tissue. 6,10 A functional role for T1R1/T1R3 activation has also been demonstrated in the gut.…”

Section: Introductionmentioning

confidence: 99%

“…A, Representative tracing illustrating the phasic contraction of the muscle strip from antrum in response to acetylcholine (ACh, 100 µmol/L) and inhibition of the amplitude and frequency of phasic contraction by MSG (100 mmol/L). Recent studies by Vancleef have identified the species-specific presence of mRNA transcripts for several types of L-AA receptors on human and mouse gastric tissues and the functional effect of their activation 16. B, Concentration-dependent inhibition of amplitude by MSG.…”

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Expression and function of umami receptors T1R1/T1R3 in gastric smooth muscle

Wang

Blakeney

Mahavadi

et al. 2019

Neurogastroenterology Motil

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Background: l-amino acids, such as monosodium glutamate (MSG), activate the umami receptor T1R1/T1R3. We previously showed increased peristalsis in response to activation of T1R1/T1R3 by MSG in mouse colon. However, the expression and function of these receptors in the different regions of the stomach are not clear. Methods: Mouse gastric smooth muscle cells (SMCs) were isolated and cultured in Dulbecco's Modified Eagle Medium. Expression of T1R1 and T1R3 was measured by RT-PCR and Western blot. The effect of MSG with and without inosine monophosphate (IMP, an allosteric activator of T1R1/T1R3) on acetylcholine (ACh)-induced contraction was measured in muscle strips and isolated SMCs by scanning micrometry. The effect of MSG with or without IMP on activation of G proteins and ACh-induced Ca 2+ release was measured in SMCs. Key Results: Monosodium glutamate inhibited ACh-induced contractions in muscle strips from both antrum and fundus and the effect of MSG was augmented by IMP; the effects were concentration-dependent and not affected by the nitric oxide synthase inhibitor, L-NNA, or tetrodotoxin suggesting a direct effect on SMCs. In isolated gastric SMCs, T1R1 and T1R3 transcripts and protein were identified. Addition of MSG with or without IMP inhibited ACh-induced Ca 2+ release and muscle contraction; the effect on contraction was blocked by pertussis toxin suggesting activation of Gα i proteins. MSG in the presence of IMP selectively activated Gα i2 . Conclusions and Inferences: Umami receptors (T1R1/T1R3) are present on SMCs of the stomach, and activation of these receptors induces muscle relaxation by decreasing [Ca 2+ ] i via Gα i2 . K E Y W O R D S cellular signalling, gastric motility, smooth muscle, taste receptors, umami

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Obesity Impairs Oligopeptide/Amino Acid‐Induced Ghrelin Release and Smooth Muscle Contractions in the Human Proximal Stomach

Abstract: Region-specific targeting of AA taste receptors on both enteroendocrine and SM cells with specific AA-enriched diets might be a useful strategy to combat obesity as well as hypomotility disorders.

Cited by 17 publications

References 49 publications

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

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

A role for taste receptors in (neuro)endocrinology?

Expression and function of umami receptors T1R1/T1R3 in gastric smooth muscle

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