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Central actions of ...
Central actions of glucagon-like peptide-1 on food intake and reward: Novel neurological targets and sex divergent effects
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- Richard, Jennifer E. (författare)
- 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)
- ISBN 9789178335077
- Göteborgs universitet, 2019
- Engelska.
- Relaterad länk:
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https://gup.ub.gu.se...
Abstract
Ämnesord
Stäng
- Obesity is one of the biggest health risks of our society; however, treatment options are sparse and often result in suboptimal weight-loss. The glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonist liraglutide was recently approved for treatment of obesity in the US. GLP-1, and synthetic analogues, reduce body weight by suppressing food intake and food reward through actions on GLP-1Rs in the CNS. Regulation of homeostatic and hedonic feeding, by GLP-1, was previously attributed to actions specifically within the hypothalamus or limbic system, respectively. Our studies chal-lenge this view and demonstrate novel central areas mediating the effects of GLP-1R stimulation on food intake and reward. Using standard food intake and body weight measurements, and reward behavior tests, we demonstrate that GLP-1R stimulation, using GLP-1R agonist exendin-4 (Ex4), reduces food intake and food reward behavior through actions in the nucleus of the solitary tract (NTS) and lateral hypothalamus (LH). In addition, NTS GLP-1 neurons were found in close proximity to noradrenergic neurons, and intra-NTS Ex4 injection increased dopamine-related genes in the ventral tegmental area, suggesting a link between the NTS and the reward system. Furthermore, the parabrachial nucleus (PBN) was identified as a novel area mediating the anorexic effects of GLP-1R stimulation. This thesis also demonstrates potential sex differences in the effects of GLP-1, and its agonists, as central GLP-1R stimulation suppresses food-motivated behavior to a larger degree in females compared to males. In addition, central estrogen, and estrogen receptor-α (ERα), blockade attenuate the effects of Ex4 on food reward, but not food intake. However, specifically within the LH, GLP-1R stimulation is sufficient to reduce food-motivated behavior in both sexes, while it is only necessary in males. In conclusion, effects of GLP-1R stimulation on food intake and food reward are not bound to actions on GLP-1Rs exclusively within homeostatic or hedonic feeding cen-ters. Furthermore, GLP-1-mediated food reward, but not food intake, suppression is dependent on estrogen signaling. However, GLP-1 may also act differently within specific brain nuclei, as LH GLP-1R stimulation is sufficient to reduce food-reward in both sexes, while it is only necessary for its actions in males.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Nyckelord
- Glucagon-like peptide-1
- Food reward
- Food intake
- GLP-1
- Sex differences
Publikations- och innehållstyp
- vet (ämneskategori)
- dok (ämneskategori)
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