The Translational Genomics Study on the Gene Expression of Lipid Metabolism Induced by High-Fat Diet in Obesity Based on Bioinformatics

doi:10.3877/cma.j.issn.2095-9605.2025.02.004

Abstract

Abstract:

Objective

This study aimed to investigate the physiological and metabolic changes induced by a high-fat diet in mice using bioinformatics methods, and to reveal the underlying molecular interaction mechanisms through systematic analysis of differential gene expression.

Methods

Gene expression data were retrieved from the GEO database, and the chip dataset GSE136821 was selected for analysis. Differentially expressed genes (DEGs) in mouse liver tissue were identified using several Bioconductor R packages (such as org.Mm.eg.db, Limma, and clusterProfiler). GO functional annotation and KEGG pathway enrichment analyses were performed on these DEGs. The top 200 DEGs were further used to construct a protein–protein interaction (PPI) network via the STRING online database, and high-degree hub genes were subsequently identified using Cytoscape.

Results

A total of 1 169 DEGs were identified, with 755 genes upregulated and 414 genes downregulated in the high-fat diet group. GO enrichment analysis revealed that these DEGs are involved in biological processes such as lipid metabolism, fatty acid metabolism, and regulation of inflammatory responses, and they exhibit various molecular functions including NAD(P)⁺ nucleosidase activity, lipase activity, and lipid transporter activity. KEGG pathway analysis further demonstrated significant enrichment of DEGs in several key biological pathways, notably the PI3K-Akt signaling pathway, PPAR signaling pathway, and cholesterol metabolism-related pathways. PPI network analysis further identified PPARγ, Src, and Manf as critical regulatory nodes, suggesting their important roles in high-fat diet-induced obesity and lipid metabolism dysregulation.

Conclusions

A high-fat diet significantly alters the expression of genes related to lipid metabolism and inflammatory regulation in the mouse liver. Key genes such as PPARγ, Src, and Manf interact to form a complex regulatory network.

Key words: Bioinformatics, Obesity, Lipid metabolism, Differential gene

Zhong Ren, Mengyuan Luo, Zehui Yan. The Translational Genomics Study on the Gene Expression of Lipid Metabolism Induced by High-Fat Diet in Obesity Based on Bioinformatics[J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2025, 11(02): 104-110.

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References 25

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序号	GO索引号	GO名称	基因数目
1	GO:0019216	regulation of lipid metabolic process	52
2	GO:0032496	response to lipopolysaccharide	52
3	GO:0045089	positive regulation of innate immune response	33
4	GO:0050727	regulation of inflammatory response	64
5	GO:0019369	arachidonic acid metabolic process	28
6	GO:0006631	fatty acid metabolic process	78
7	GO:0001676	long-chain fatty acid metabolic process	39
8	GO:1903555	regulation of tumor necrosis factor superfamily cytokine production	56
9	GO:0032103	positive regulation of response to external stimulus	92
10	GO:0050900	leukocyte migration	84

序号	GO索引号	GO名称	基因数目
1	GO:0019216	regulation of lipid metabolic process	52
2	GO:0032496	response to lipopolysaccharide	52
3	GO:0045089	positive regulation of innate immune response	33
4	GO:0050727	regulation of inflammatory response	64
5	GO:0019369	arachidonic acid metabolic process	28
6	GO:0006631	fatty acid metabolic process	78
7	GO:0001676	long-chain fatty acid metabolic process	39
8	GO:1903555	regulation of tumor necrosis factor superfamily cytokine production	56
9	GO:0032103	positive regulation of response to external stimulus	92
10	GO:0050900	leukocyte migration	84

序号	GO索引号	GO名称	基因数目
1	GO:0016298	lipase activity	15
2	GO:0005324	long-chain fatty acid transporter activity	5
3	GO:0005504	fatty acid binding	13
4	GO:0015245	fatty acid transmembrane transporter activity	6
5	GO:0050135	NAD(P)⁺ nucleosidase activity	7
6	GO:0034185	apolipoprotein binding	9
7	GO:0120319	long-chain fatty acid omega-1 hydroxylase activity	9
8	GO:0005319	lipid transporter activity	31
9	GO:0051861	glycolipid binding	13
10	GO:0016712	oxidoreductase activity	30

序号	GO索引号	GO名称	基因数目
1	GO:0016298	lipase activity	15
2	GO:0005324	long-chain fatty acid transporter activity	5
3	GO:0005504	fatty acid binding	13
4	GO:0015245	fatty acid transmembrane transporter activity	6
5	GO:0050135	NAD(P)⁺ nucleosidase activity	7
6	GO:0034185	apolipoprotein binding	9
7	GO:0120319	long-chain fatty acid omega-1 hydroxylase activity	9
8	GO:0005319	lipid transporter activity	31
9	GO:0051861	glycolipid binding	13
10	GO:0016712	oxidoreductase activity	30

序号	Pathway索引号	Pathway名称	基因数目
1	mmu05418	atherosclerosis	22
2	mmu04151	PI3K-Akt signaling pathway	45
3	mmu05417	Lipid and atherosclerosis	33
4	mmu04979	Cholesterol metabolism	12
5	mmu04064	NF-kappa B signaling pathway	20
6	mmu03320	PPAR signaling pathway	18
7	mmu04933	AGE-RAGE signaling pathway in diabetic complications	22
8	mmu04750	Inflammatory mediator regulation of TRP channels	26
9	mmu04060	Cytokine-cytokine receptor interaction	48
10	mmu00590	Arachidonic acid metabolism	24

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