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Glucagon-Like Pepti...
Glucagon-Like Peptide 1 and Its Analogs Act in the Dorsal Raphe and Modulate Central Serotonin to Reduce Appetite and Body Weight
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- Anderberg, Rozita H, 1976 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- Richard, Jennifer E. (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- Eerola, Kim, 1982 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- López-Ferreras, Lorena (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- Banke, Elin (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- Hansson, Caroline, 1981 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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- Nissbrandt, Hans, 1952 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology
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- Bergquist, Filip, 1970 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology
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Gribble, F. M. (author)
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Reimann, F. (author)
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- Wernstedt Asterholm, Ingrid, 1978 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Lamy, C. M. (author)
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- Skibicka, Karolina P (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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(creator_code:org_t)
- 2017-01-05
- 2017
- English.
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:4, s. 1062-1073
- Related links:
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https://diabetes.dia...
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https://gup.ub.gu.se...
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https://doi.org/10.2...
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Abstract
Subject headings
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- Glucagon-like peptide 1 (GLP-1) and serotonin play critical roles in energy balance regulation. Both systems are exploited clinically as antiobesity strategies. Surprisingly, whether they interact in order to regulate energy balance is poorly understood. Here we investigated mechanisms by which GLP-1 and serotonin interact at the level of the central nervous system. Serotonin depletion impaired the ability of exendin-4, a clinically used GLP-1 analog, to reduce body weight in rats, suggesting that serotonin is a critical mediator of the energy balance impact of GLP-1 receptor (GLP-1R) activation. Serotonin turnover and expression of 5-hydroxytryptamine (5-HT) 2A (5-HT2A) and 5-HT2C serotonin receptors in the hypothalamus were altered by GLP-1R activation. We demonstrate that the 5-HT2A, but surprisingly not the 5-HT2C, receptor is critical for weight loss, anorexia, and fat mass reduction induced by central GLP-1R activation. Importantly, central 5-HT2A receptors are also required for peripherally injected liraglutide to reduce feeding and weight. Dorsal raphe (DR) harbors cell bodies of serotonin-producing neurons that supply serotonin to the hypothalamic nuclei. We show that GLP-1R stimulation in DR is sufficient to induce hypophagia and increase the electrical activity of the DR serotonin neurons. Finally, our results disassociate brain metabolic and emotionality pathways impacted by GLP-1R activation. This study identifies serotonin as a new critical neural substrate for GLP-1 impact on energy homeostasis and expands the current map of brain areas impacted by GLP-1R activation.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- Aminopyridines/pharmacology
- Animals
- Anorexia
- Appetite/*drug effects
- Body Weight/*drug effects
- Dorsal Raphe Nucleus/*metabolism
- Feeding Behavior/drug effects
- Fenclonine/pharmacology
- Glucagon-Like Peptide 1/*pharmacology
- Glucagon-Like Peptide-1 Receptor/*drug effects/metabolism
- Hypoglycemic Agents/*pharmacology
- Indoles/pharmacology
- Liraglutide/pharmacology
- Male
- Peptides/pharmacology
- Pyrrolidines/pharmacology
- Rats
- Rats
- Sprague-Dawley
- Receptor
- Serotonin
- 5-HT2A/*drug effects/metabolism
- Receptor
- Serotonin
- 5-HT2C/*drug effects/metabolism
- Serotonin/*metabolism
- Serotonin Antagonists/pharmacology
- Venoms/pharmacology
- Weight Loss/drug effects
Publication and Content Type
- ref (subject category)
- art (subject category)
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Diabetes
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- By the author/editor
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Anderberg, Rozit ...
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Richard, Jennife ...
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Eerola, Kim, 198 ...
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López-Ferreras, ...
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Banke, Elin
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Hansson, Carolin ...
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show more...
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Nissbrandt, Hans ...
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Bergquist, Filip ...
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Gribble, F. M.
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Reimann, F.
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Wernstedt Asterh ...
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Lamy, C. M.
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Skibicka, Karoli ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
- Articles in the publication
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Diabetes
- By the university
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University of Gothenburg