engleski

Effect of high fat – high sugar diet and antidiabetic treatment on the rat liver transcriptome

Aim: The aim of this study was to investigate changes in the male and female rat liver transcriptome as a consequence of high-fat-high- sugar (HFHS) diet and treatment with metformin and liraglutide. Material and methods: Gene expression was analysed in rat livers on a HFHS diet and in rat livers treated with metformin and liraglutide. We analysed 3-4 samples per group and 500 ng of total RNA per sample was used for analyses with rat Clariom™ S Assay (Applied Biosystems). The procedure was done by following the manufacturer’s instructions. Briefly, after overnight hybridization microarrays were washed and stained using GeneChip Fluidics Station 450 and scanned on a Affymetrix GeneChip Scanner 3000 7G. Results: Considering all samples, comparison between males and females (including both diets and all three treatments) resulted in 757 DE genes, 26 enriched KEGG pathways and 34 TFs. A strong interaction was observed between gender and liraglutide treatment on the HFHS diet, where over 2000 DE genes and 131 KEGG pathways responded differently to liraglutide treatment based on gender ; there were no changes related to metformin treatment. Discussion and conclusions: HFHS diet given to both sexes did not affect changes in the liver transcriptome in DEGs, KEGG pathways, and a single enriched TF. Liraglutide antidiabetic treatment has a sex specific effect on the rat liver transcriptome, with a strong effect on the male liver transcriptome but no change in the female liver. Source(s) of research support: Bohdan Malaniak Cedars-Sinai–RECOOP Young Scientists Research Grant (RECOOP Grant # 003 2016 Cosic - Drenjancevic. Osijek, Croatia, “The role of oxidative stress in development of impaired vascular response in obese pre-diabetic elderly rats of both sexes treated with metformin or liraglutide”). Also, this work has partly been supported by the Croatian Science Foundation under the project HRZZ-IP-2014-09-2324 and internal funding project of the University of Osijek (UNISO-ZUP 2018-68). Ethical Committee Approval: Experimental procedures conformed with the European Guidelines for the Care and Use of Laboratory Animals (directive 2010/63/EU) and have been approved by the local Ethical Committee (Faculty of Medicine, University of Osijek, class: 602-04/ 16-08/15, no. 2158-61-07-16-14). 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 (CRRCs).

Liver, transcriptome, diet, metformin, liraglutide, rat

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