Gastric ghrelin, <scp>GOAT</scp>, leptin, and leptinR expression as well as peripheral serotonin are dysregulated in humans with obesity

Ritze, Yvonne; Schollenberger, Asja E.; Sinno, Maria Hamze; Bühler, Nicola Elena Maria; Böhle, Maureen; Bárdos, Gyöngyi; Sauer, Helene; Mack, Isabelle; Enck, Paul; Zipfel, Stephan; Meile, Tobias; Königsrainer, Alfred; Kramer, Matthew; Bischoff, Stephan C.

doi:10.1111/nmo.12773

Cited by 22 publications

(18 citation statements)

References 47 publications

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“…An increased number of ghrelin positive cells has previously been reported in the gastric corpus of obese patients . We only observed an increase in ghrelin tissue content in the antrum of obese patients.…”

Section: Discussionsupporting

confidence: 48%

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

Vancleef

Thijs

Baert

et al. 2018

Molecular Nutrition Food Res

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Section: Discussionsupporting

confidence: 48%

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

Vancleef

Thijs

Baert

et al. 2018

Molecular Nutrition Food Res

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“…This is accompanied by ghrelin resistance in neural circuits that regulate energy homeostasis, which protects the body from a higher body weight set-point during excessive food availability (38). Contradictory findings have been reported on the effect of obesity on ghrelin mRNA expression, or the number of ghrelin-positive cells in biopsies (39)(40)(41)(42). Our study in primary fundic cultures from whole stomach samples from multiorgan donors and obese patients undergoing bariatric surgery provide a more elegant model to study the mechanisms involved.…”

Section: Discussionmentioning

confidence: 74%

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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“…Work by Hernandez et al (2012) demonstrated that administration of a HFD to lactating rats increased the mRNA expression of Tph1 in the mammary gland, along with elevated levels of inflammatory marker Tnfa [22]. Finally, obese patients have demonstrated reduced circulating serotonin concentrations relative to non-obese patients, potentially resulting in reduced lipolysis and increased lipid storage [23]. Additionally, numerous pharmacotherapies used in the treatment of obesity manipulate both the central and peripheral serotonin systems [24].…”

Section: Introductionmentioning

confidence: 99%

Serotonin Deficiency Rescues Lactation on Day 1 in Mice Fed a High Fat Diet

Weaver¹,

Bohrer²,

Prichard³

et al. 2016

PLoS ONE

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Obesity is an inflammatory state associated with delayed lactogenesis stage II and altered mammary gland morphology. Serotonin mediates inflammation and mammary gland involution. The objective of this study was to determine if a genetic deficiency of tryptophan hydroxylase 1, the rate-limiting enzyme in peripheral serotonin synthesis, would result in an improved ability to lactate in dams fed a high fat diet. Twenty-six female mice were fed a high (HFD) or low fat (LFD) diet throughout pregnancy and lactation. Fourteen mice were genetically deficient for Tph1 (Tph1-/-), and twelve were wild type. Milk yield, pup mortality, and dam weights were recorded and milk samples were collected. On day 10 of lactation, dams were sacrificed and mammary glands were harvested for RT-PCR and histological evaluation. HFD dams weighed more than LFD dams at the onset of lactation. WT HFD dams were unable to lactate on day 1 of lactation and exhibited increased pup mortality relative to all other treatments, including Tph1-/- HFD dams. mRNA expression of immune markers C-X-C motif chemokine 5 and tumor necrosis factor alpha were elevated in WT HFD mammary glands. Mammary gland histology showed a reduced number of alveoli in WT compared to Tph1-/- dams, regardless of diet, and the alveoli of HFD dams were smaller than those of LFD dams. Finally, fatty acid profile in milk was dynamic in both early and peak lactation, with reduced de novo synthesis of fatty acids on day 10 of lactation in the HFD groups. Administration of a HFD to C57BL/6 dams produced an obese phenotype in the mammary gland, which was alleviated by a genetic deficiency of Tph1. Serotonin may modulate the effects of obesity on the mammary gland, potentially contributing to the delayed onset of lactogenesis seen in obese women.

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Gastric ghrelin, GOAT, leptin, and leptinR expression as well as peripheral serotonin are dysregulated in humans with obesity

Abstract: Our data indicate that obesity causes a dysregulation of gastrointestinal hormones at the tissue level and serum, including a negative correlation with an increased marker of subclinical inflammation.

Cited by 22 publications

References 47 publications

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

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

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

Serotonin Deficiency Rescues Lactation on Day 1 in Mice Fed a High Fat Diet

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