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High-fat high-sugar diet and Liraglutide treatment introduce sex specific changes of adipocytokine receptors in the rat brain while Metformin has similar effect on both sexes

INTRODUCTION. Chronic overnutrition contributes to chronic conditions such as obesity, diabetes type 2 or neurodegeneration via disruption of hypothalamic pathways in charge of homeostasis maintenance. The aim of this study was to evaluate influence of diet rich in carbohydrates and fat (HFHS) and the influence of selected antidiabetic drugs on the brain of adult Sprague-Dawley rats. METHODS. Sixty four (N♂=32, N♀=32) Sprague-Dawley rats, 44 weeks old, were separated in 4 groups: 1. Standard diet (SD), 2. HFHS, 3. HFHS + metformin 4. HFHS + liraglutide. Obesity was induced in groups 2, 3, and 4 during first 5 weeks of experiment, followed with 15-week long metformin and liraglutide treatment of groups 3 and 4. The brains were collected and free-floating immunohistochemistry was performed using antibodies for following receptors: insulin (IR- α), leptin (ObR), insulin-like growth factor 1 (IGF-1Rβ) and kisspeptin (Kiss1R). Hippocampus (HIPP) and hypothalamus (HTH) were analysed. RESULTS. Hypothalamic regulation of satiety under HFHS diet is mostly regulated by upregulation of ObR and IGF in lateral hypothalamus (HTH-LH) of male rats. The same diet introduces more complex change in female hypothalamus: upregulation of Kiss1R in arcuatus (HTH-ARC), downregulation of IR-α and IGF-1Rβ in HTH-LH. Males responded to HFHS diet with upregulation of ObR in all hippocampal regions while female respond was mostly downregulation of all observed receptors. Metformin therapy had almost similar effect in both sexes ; general upregulation of ObR and IR-α and no effect on Kiss1R. Liraglutide therapy resulted almost the same in males, with exception of downregulation of Kiss1R in hippocampus. Female response on liraglutide was downregulation of IR-α in satiety centers. DISCUSSION AND CONCLUSION. HFHS diet itself has sex specific effect on expression of adipocytokine receptors in satiety centres. While metformin affect both sexes similary, liraglutide had more complex effect on female brain what is reflected in over-eating.

obesity, diabetes, brain, rat, adipocytokines receptors

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