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Diet-induced obesity causes ghrelin resistance in reward processing tasks

journal contribution
posted on 2024-11-01, 23:10 authored by Sarah Lockie, Tara Dinan, Andrew Lawrence, Sarah SpencerSarah Spencer, Z.B Andrews
Diet-induced obesity (DIO) causes ghrelin resistance in hypothalamic Agouti-related peptide (AgRP) neurons. However, ghrelin promotes feeding through actions at both the hypothalamus and mesolimbic dopamine reward pathways. Therefore, we hypothesized that DIO would also establish ghrelin resistance in the ventral tegmental area (VTA), a major site of dopaminergic cell bodies important in reward processing. We observed reduced sucrose and saccharin consumption in Ghrelin KO vs Ghrelin WT mice. Moreover, DIO reduced saccharin consumption relative to chow-fed controls. These data suggest that the deletion of ghrelin and high fat diet both cause anhedonia. To assess if these are causally related, we tested whether DIO caused ghrelin resistance in a classic model of drug reward, conditioned place preference (CPP). Chow or high fat diet (HFD) mice were conditioned with ghrelin (1. mg/kg in 10. ml/kg ip) in the presence or absence of food in the conditioning chamber. We observed a CPP to ghrelin in chow-fed mice but not in HFD-fed mice. HFD-fed mice still showed a CPP for cocaine (20. mg/kg), indicating that they maintained the ability to develop conditioned behaviour. The absence of food availability during ghrelin conditioning sessions induced a conditioned place aversion, an effect that was still present in both chow and HFD mice. Bilateral intra-VTA ghrelin injection (0.33. μg/μl in 0.5. μl) robustly increased feeding in both chow-fed and high fat diet (HFD)-fed mice; however, this was correlated with body weight only in the chow-fed mice. Our results suggest that DIO causes ghrelin resistance albeit not directly in the VTA. We suggest there is impaired ghrelin sensitivity in upstream pathways regulating reward pathways, highlighting a functional role for ghrelin linking appropriate metabolic sensing with reward processing.

History

Journal

Psychoneuroendocrinology

Volume

62

Start page

114

End page

120

Total pages

7

Publisher

Elsevier

Place published

United Kingdom

Language

English

Copyright

© 2015 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license

Former Identifier

2006059216

Esploro creation date

2020-06-22

Fedora creation date

2016-03-04

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