INTRODUCTION and OBJECTIVE: C57BL/6J mouse strain is known to be susceptible to obesity and/or diabetes/ metabolic syndrome after a high-fat diet term. However, cellular mechanism to transformation into obesity is not fully understood yet. In addition to clinical studies, recent evidences indicate hope for cellular pathophysiology from in silico analysis. The aim of this study was to detect possible pathophysiological factors in diet-induced obesity on examining the expression levels of genes by using bioinformatics tools. METHODS: GSE395491 dataset obtained from GEO (Gene Expression Omnibus) database was re-examined for this research. In the dataset, total RNA obtained from isolated liver tissues of C57BL/6J mice fed normal diet (27 samples) and high fat diet (24 samples) is recruited. After the gene expression levels in the dataset were re-analysed in the R program, gene set enrichment analyses were performed in Gene Ontology (GO) and ENRICHR tools. APPROACH FOR STATISTICAL ANALYSIS: Expression levels of genes, commonly implicated to play a role in several biological processes, in GSE39549 dataset are re-analysed in R program. Based on Benjamini-Hochberg correction, adjusted p-values <0.05 were accepted as significant. RESULTS and CONCLUSION: Gene expression levels indicated that BCL2 (B-cell lymphoma 2), CASP-1,4,6,7 (caspases), MCL1 (myeloid cell leukemia 2), BIRC2 (baculoviral IAP repeat-containing protein 2) [responsible for apoptosis] and TNF (tumor necrosis factor), TNFSF-10,13B (TNF superfamily members), TNFRSF-1B,8,10,11A,18,21,22 (TNF receptor superfamily members), TNFAIP-2,3,8 (TNF alpha induced proteins), TLR4 (Toll-like receptor 4) [responsible for necrosis] genes were up-regulated (p<0.05) in high-fat diet group, compared with normal diet group. Although in vivo and in vitro researches about diet-induced obesity are on-going, gene expression analysis and gene set enrichment analyses results implicate that apoptotic and necrotic mechanisms may cause diet-induced obesity. Keywords: diet-induced obesity, C57BL/6J mice, apoptosis, necrosis, bioinformatics.