engleski

High-fat high-sugar diet and antidiabetic treatment affect membrane expression of leptin and insulin receptor in hippocampal cells of adult Sprague-Dawley rats

The aim of this research was to determine the submembrane localization and to quantify leptin (ObR) and insulin (IR) receptors in hippocampal cells (HIPP) of adult obese Sprague-Dawley rats in pre-diabetic state treated with two commonly used antidiabetic drugs metformin or liraglutide. Sixty four (N♂=32, N♀=32) Sprague-Dawley rats of age 44 weeks were separated in 4 groups: 1. Standard diet (SD), 2. High-fat high-sugar diet (HFHSD), 3. HFHSD + metformin (s.c., 50 mg/kg/day), 4. HFHSD + liraglutide (s.c., 0.3 mg/kg/day). The 6-week long induction of obesity in groups 2, 3, and 4 was followed with 14-week long treatment of groups 3 and 4 with metformin and liraglutide, respectively. At the end of experiment HIPP were collected and LR were isolated according to the newly adjusted protocol. Collected fractions were analysed for raft markers Flotilin-1 (Flot1) and ganglioside GM1, non- raft marker Transferrin receptor (TfR), and for ObR and IR. The LR isolation resulted with the isolates collected as 10 or 11 fractions of 1, 5 mL. It has been found that the ObR and IR are not the part of the LR in HIPP tissue. This observance was determined in all animal groups. The calorie rich diet affected receptor expression, as well as antidiabetic drugs. It has been proposed that obesity followed insulin and leptin resistance is developed because of changes in LR composition. This could also lead to impaired memory and cognitive performance. Our data suggest that ObR and IR are not part of LR in HIPP. Rather they are placed in the non-raft fractions independently from diet or treatment, but both can influence their expression. Funding: The study has been funded by RECOOP HST grant, and in part by the Croatian Science Foundation under project number IP-09-2014- 2324. Acknowledgement: This study was supported by Cedars Sinai Medical Center’s International Research and Innovation in Medicine Program, the Association for Regional Cooperation in the Fields of Health, Science and Technology (RECOOP HST Association) and the participating Cedars – Sinai Medical Center - RECOOP Research Centers (CRRC). Ethical Committee Approval: Hungarian Ethical Committee for Animal Research: registration number IV/3796/2015.

hippocampus, lipid rafts, leptin receptor, insulin receptor

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