Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Haag, M.
The effects of intranasal neuropeptide Y on high-fat diet-induced anhedonia of mice
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2023. pp. 59
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Farzi Aitak
- Holzer Peter
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- Abstract:
- Western diet contains a high percentage of saturated fatty acids and is dense in energy, which leads to overeating and the development of diet-induced obesity. There is growing evidence about the role of obesity in the development of mental health disorders such as major depression. Metabolic disturbances implicated in the development of depressive mood due to diet-induced obesity include dysregulation of the hypothalamic-pituitary-adrenal axis, release of proinflammatory cytokines, leptin and insulin resistance. In addition, both patients with depressive disorder and mouse models of high-fat diet (HFD)-induced depression show lower expression of neuropeptide Y (NPY), a peptide with antidepressant, anxiolytic and orexigenic properties. Therefore, the aim of this study was to evaluate the effect of intranasal (i.n.) NPY on HFD-induced anhedonia and its potential as a new therapeutic approach. In this study, we fed 48 male mice a HFD containing 48 kJ% of fat or control diet containing 12 kJ% of fat for a period of 8 weeks. Mice were housed in cages of two under standard laboratory conditions. Subsequently, the mice were placed in single cages in order to perform the sucrose preference test (SPT) to evaluate anhedonia. On day 2 and day 4 of SPT either NPY or sterile distilled water was applied i.n. at a dose of 100 μg. Mice were sacrificed 3 hours after the second NPY application in order to collect the brains and blood plasma samples. Brains were microdissected and the hypothalamus was used for analysis of markers of relevance. The same experiment was repeated in Y2 receptor knock-out mice. HFD reduced NPY gene expression and protein levels in the hypothalamus. Contrary to expectations, i.n. NPY reduced sucrose preference in the HFD group 3 hours after application, which is indicative of anhedonia. This effect was accompanied by lower food intake, greater weight loss and increased corticosterone levels in plasma. Sucrose preference, food intake and body weight remained unchanged in the experiment with Y2 knock-out mice. Our results are contrary to current evidence about NPY as an orexigenic and antidepressant peptide. The fact that NPY inhibited food intake and induced anhedonia in the SPT may be due to the sedative effect of NPY, which occurs at higher doses. Another possible explanation might be a desensitization to NPY by HFD. Since no effect was seen in the Y2 knock-out group, the Y2 receptor may also play a role in our observations.