Gut-brain communication by distinct sensory neurons differently controls feeding and glucose metabolism

Borgmann, Diba; Ciglieri, Elisa; Biglari, Nasim; Brandt, Claus; Cremer, Anna Lena; Backes, Heiko; Tittgemeyer, Marc; Wunderlich, Frank; Brüning, Jens C.; Fenselau, Henning

doi:10.1016/j.cmet.2021.05.002

Cited by 102 publications

(77 citation statements)

References 87 publications

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“…However, bearing in mind the caveats associated with the histology methods employed, it is possible that CCK AP/NTS neurons could also respond to GLP-1R agonists via synaptic inputs. These inputs might include vagal afferent neurons [ 7 , 30 ], AP neurons synapsing onto neighboring NTS neurons [ 31 ], as well as inputs from other central GLP-1RA-responsive cells.…”

Section: Resultsmentioning

confidence: 99%

Anorectic and aversive effects of GLP-1 receptor agonism are mediated by brainstem cholecystokinin neurons, and modulated by GIP receptor activation

Costa

Nunn

et al. 2022

Molecular Metabolism

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Objective Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective medications to reduce appetite and body weight. These actions are centrally mediated; however, the neuronal substrates involved are poorly understood. Methods We employed a combination of neuroanatomical, genetic, and behavioral approaches in the mouse to investigate the involvement of caudal brainstem cholecystokinin-expressing neurons in the effect of the GLP-1RA exendin-4. We further confirmed key neuroanatomical findings in the non-human primate brain. Results We found that cholecystokinin-expressing neurons in the caudal brainstem are required for the anorectic and body weight-lowering effects of GLP-1RAs and for the induction of GLP-1RA-induced conditioned taste avoidance. We further show that, while cholecystokinin-expressing neurons are not a direct target for glucose-dependent insulinotropic peptide (GIP), GIP receptor activation results in a reduced recruitment of these GLP-1RA-responsive neurons and a selective reduction of conditioned taste avoidance. Conclusions In addition to disclosing a neuronal population required for the full appetite- and body weight-lowering effect of GLP-1RAs, our data also provide a novel framework for understanding and ameliorating GLP-1RA-induced nausea — a major factor for withdrawal from treatment.

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Section: Resultsmentioning

confidence: 99%

Anorectic and aversive effects of GLP-1 receptor agonism are mediated by brainstem cholecystokinin neurons, and modulated by GIP receptor activation

Costa

Nunn

et al. 2022

Molecular Metabolism

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“…This phenomenon may be explained that in the early stage of AD, the Aβ 42 , especially Aβ 42 monomers or small oligomers from the brain and blood pools, can be easily transmitted through the enteric nervous system (ENS) to the digestive tract of the stomach and intestines. According to reports, the colon contains the most neurons (Gershon, 1998;Rao and Gershon, 2016;Brierley et al, 2018;Borgmann et al, 2021), and the monomers that gradually accumulate in the colon can be aggregated into small molecular weight oligomers. It is worth noting that the colon undergoes vital processes to ensure our health.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Changes in the Levels of Amyloid-β42 Species in the Brain and Periphery of APP/PS1 Mice and Their Significance for Alzheimer’s Disease

Zhang

Yang

et al. 2021

Front. Mol. Neurosci.

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Although amyloid-β42 (Aβ42) has been used as one of the core biomarkers for Alzheimer’s disease (AD) diagnosis, the dynamic changes of its different forms in the brain, blood, and even intestines and its correlation with the progression of AD disease remain obscure. Herein, we screened Aβ42-specific preferred antibody pairs 1F12/1F12 and 1F12/2C6 to accurately detect Aβ42 types using sandwich ELISA, including total Aβ42, Aβ42 oligomers (Aβ42Os), and Aβ42 monomers (Aβ42Ms). The levels of Aβ42 species in the brain, blood, and intestines of different aged APP/PS1 mice were quantified to study their correlation with AD progression. Total Aβ42 levels in the blood were not correlated with AD progression, but Aβ42Ms level in the blood of 9-month-old APP/PS1 mice was significantly reduced, and Aβ42Os level in the brain was significantly elevated compared to 3-month-old APP/PS1, demonstrating that the levels of Aβ42Ms and Aβ42Os in the blood and brain were correlated with AD progression. Interestingly, in 9-month-old APP/PS1 mice, the level of Aβ42 in the intestine was higher than that in 3-month-old APP/PS1 mice, indicating that the increased level of Aβ42 in the gastrointestinal organs may also be related to the progression of AD. Meanwhile, changes in the gut microbiota composition of APP/PS1 mice with age were also observed. Therefore, the increase in Aβ derived from intestinal tissues and changes in microbiome composition can be used as a potential early diagnosis tool for AD, and further used as an indicator of drug intervention to reduce brain amyloid.

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“…The second mode of communication could be due to the existence of GLP-1 receptors on vagal afferent sensitive neurons in the gut. Indeed, Borgmann et al [ 19 ] have shown that the chemogenetic activation of GLP-1 receptor in the intestine reduces glucose levels. Third, GLP-1 receptors are implicated in the activation of hepatic portal vein glucose sensors leading to a decrease in glycemia via an afferent nervous message [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

High Hydrostatic Pressure Processing of Human Milk Increases Apelin and GLP-1 Contents to Modulate Gut Contraction and Glucose Metabolism in Mice Compared to Holder Pasteurization

et al. 2022

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Background: High hydrostatic pressure (HHP) processing is a non-thermal method proposed as an alternative to Holder pasteurization (HoP) for the sterilization of human breast milk (BM). HHP preserves numerous milk bioactive factors that are degraded by HoP, but no data are available for milk apelin and glucagon-like peptide 1 (GLP-1), two hormones implicated in the control of glucose metabolism directly and via the gut–brain axis. This study aims to determine the effects of HoP and HHP processing on apelin and GLP-1 concentrations in BM and to test the effect of oral treatments with HoP- and HHP-BM on intestinal contractions and glucose metabolism in adult mice. Methods: Mice were treated by daily oral gavages with HoP- or HHP-BM during one week before intestinal contractions, and glucose tolerance was assessed. mRNA expression of enteric neuronal enzymes known to control intestinal contraction was measured. Results: HoP-BM displayed a reduced concentration of apelin and GLP-1, whereas HHP processing preserved these hormones close to their initial levels in raw milk. Chronic HHP-BM administration to mice increased ileal mRNA nNos expression level leading to a decrease in gut contraction associated with improved glucose tolerance. Conclusion: In comparison to HoP, HPP processing of BM preserves both apelin and GLP-1 and improves glucose tolerance by acting on gut contractions. This study reinforces previous findings demonstrating that HHP processing provides BM with a higher biological value than BM treated by HoP.

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Gut-brain communication by distinct sensory neurons differently controls feeding and glucose metabolism

Cited by 102 publications

References 87 publications

Anorectic and aversive effects of GLP-1 receptor agonism are mediated by brainstem cholecystokinin neurons, and modulated by GIP receptor activation

Anorectic and aversive effects of GLP-1 receptor agonism are mediated by brainstem cholecystokinin neurons, and modulated by GIP receptor activation

Dynamic Changes in the Levels of Amyloid-β42 Species in the Brain and Periphery of APP/PS1 Mice and Their Significance for Alzheimer’s Disease

High Hydrostatic Pressure Processing of Human Milk Increases Apelin and GLP-1 Contents to Modulate Gut Contraction and Glucose Metabolism in Mice Compared to Holder Pasteurization

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