Hindbrain nucleus tractus solitarius glucagon-like peptide-1 receptor signaling reduces appetitive and motivational aspects of feeding

Alhadeff, Amber L.; Grill, Harvey J.

doi:10.1152/ajpregu.00179.2014

Cited by 85 publications

(70 citation statements)

References 28 publications

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“…Pharmacological activation of was a change similar to that elicited by cholecystokinin (CCK) and leptin, endogenously expressed peptides shown to modulate the activity of GCG neurons (39,40). The action potential firing frequency in unlabeled neurons was not affected by CNO perfusion We then tested whether GCG neuronal activacentral GLP-1Rs has clearly been shown to lead to a reduction in food intake (7,15,17,20,26,(41)(42)(43)(44)(45). To examine whether central GCG neuron activation is sufficient to reduce feeding, we stimulated GCG neurons in fed and fasted animals and measured chow food and high-calorie diet (HCD) intake.…”

Section: Resultsmentioning

confidence: 99%

Activation of murine pre-proglucagon–producing neurons reduces food intake and body weight

Gaykema

Newmyer

Ottolini

et al. 2017

Journal of Clinical Investigation

108

156

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Statistics. All data were subjected to statistical analysis in GraphPad Prism 6. When WT and transgene GCG-Gq DREADD mice were compared, 2-tailed unpaired t tests were performed. Time course tests were analyzed with 2-way repeated measures ANOVA with treatment and time points as independent variables. When the same mice received alternating CNO and saline treatments, paired 2-tailed t tests were used to evaluate data for significance. Data from once-performed behavioral tests, such as the open field and elevated plus maze, were analyzed with unpaired 2-tailed t tests. Data are expressed as mean ± SEM. Statistical significance was considered with P < 0.05.Study approval. All animal procedures were approved by the Institutional Animal Care and Use Committee of the University of Virginia and conducted in accordance with its guidelines.

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Section: Resultsmentioning

confidence: 99%

Activation of murine pre-proglucagon–producing neurons reduces food intake and body weight

Gaykema

Newmyer

Ottolini

et al. 2017

Journal of Clinical Investigation

108

156

View full text Add to dashboard Cite

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“…The stimulatory effects of leptin on VTA function are mediated via LepRb neurons in the LHA, which innervate the VTA [75]. Finally, recent data demonstrated that the above mentioned homeo-static and anorexic aspects of feeding substantially interact with hedonic feeding paradigms [79,80], and complex behaviors like feeding should be understood as an integration of distinct feeding behaviors [81] (Fig. 3C).…”

Section: Leptin and Central Control Of Energy Homeostasismentioning

confidence: 99%

Structure, production and signaling of leptin

Münzberg¹,

Morrison²

2015

Metabolism

360

261

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The cloning of leptin in 1994 was an important milestone in obesity research. In those days obesity was stigmatized as a condition caused by lack of character and self-control. Mutations in either leptin or its receptor were the first single gene mutations found to cause morbid obesity, and it is now appreciated that obesity is caused by a dysregulation of central neuronal circuits. From the first discovery of the leptin deficient obese mouse (ob/ob), to the cloning of leptin (ob aka lep) and leptin receptor (db aka lepr) genes, much has been learned about leptin and its action in the central nervous system. The initial high hopes that leptin would cure obesity were quickly dampened by the discovery that most obese humans have increased leptin levels and develop leptin resistance. Nevertheless, leptin target sites in the brain represent an excellent blueprint for distinct neuronal circuits that control energy homeostasis. A better understanding of the regulation and interconnection of these circuits will further guide and improve the development of safe and effective interventions to treat obesity. This review will highlight our current knowledge about the hormone leptin, its signaling pathways and its central actions to mediate distinct physiological functions.

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“…Recent evidence has shown that GLP-1R activation in nuclei like the NTS, historically a nucleus believed to solely regulate homeostatic or non-reward related feeding, can also suppress motivation to eat and the rewarding value of food (as measured by progressive ratio operant responding and conditioned place preference, respectively)[32,33]. The mechanisms for this reward-suppression are still unclear.…”

Section: Central Actions Of Glp-1 On Food and Drug Rewardsmentioning

confidence: 99%

GLP-1 influences food and drug reward

Hayes¹,

Schmidt

2016

Current Opinion in Behavioral Sciences

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Natural rewards, including food, water, sleep and social interactions, are required to sustain life. The neural substrates that regulate the reinforcing effects of these behaviors are also the same neurobiological mechanisms mediating mood, motivation and the rewarding effects of pharmacological stimuli. That the neuropeptide glucagon-like peptide-1 (GLP-1) is under investigation for both the homeostatic and hedonic controls of feeding is not surprising or novel. However, if the neural substrates that underline food reward are shared with other reward-related behaviors generally, then future research should investigate and embrace the likelihood that endogenous and exogenous GLP-1 receptor activation may influence multiple reward-related behaviors. Indeed, studies of the neurobiological mechanisms underlying motivated feeding behavior have informed much of the basic research investigating neural substrates of drug addiction. An emerging literature demonstrates a role for the GLP-1 system in modulating maladaptive reward behaviors, including drug and alcohol consumption. Thus, if GLP-1-based pharmacotherapies are to be used to treat drug addiction and other diseases associated with maladaptive reward behaviors (e.g. obesity and eating disorders), the neuroscience field must conduct systematic, mechanistic neuropharmacological and behavioral studies of each GLP-1 receptor-expressing nucleus within the brain. It is possible that behavioral selectivity may result from these studies, which could inform future approaches to targeting GLP-1R signaling in discrete brain nuclei to treat motivated behaviors. Equally as likely, non-selective effects on natural reward and maladaptive reward behaviors may be observed for GLP-1-based pharmacotherapies. In this case, a better understanding of the effects of increased central GLP-1R activation on motivated behaviors will aid in clinical approaches toward treating aberrant feeding behaviors and/or drug dependence.

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Hindbrain nucleus tractus solitarius glucagon-like peptide-1 receptor signaling reduces appetitive and motivational aspects of feeding

Cited by 85 publications

References 28 publications

Activation of murine pre-proglucagon–producing neurons reduces food intake and body weight

Activation of murine pre-proglucagon–producing neurons reduces food intake and body weight

Structure, production and signaling of leptin

GLP-1 influences food and drug reward

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