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Network-Based Association Study of Obesity and Type 2 Diabetes with Gene Expression Profiles.

Zhang S, Wang B, Shi J, Li J - Biomed Res Int (2015)

Bottom Line: However, the molecular mechanisms of the disease relations are not well discovered yet.As a conclusion, our network-based method not only gives better support for the close connection between obesity and T2D, but also provides a systemic view in understanding the molecular functions underneath the links.It should be helpful in the development of new therapies for obesity, T2D, and the associated diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioinformatics & Biostatistics, School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

ABSTRACT
The increased prevalence of obesity and type 2 diabetes (T2D) has become an important factor affecting the health of the human. Obesity is commonly considered as a major risk factor for the development of T2D. However, the molecular mechanisms of the disease relations are not well discovered yet. In this study, the combination of multiple differential expression profiles and a comprehensive biological network of obesity and T2D allowed us to identify and compare the disease-responsive active modules and subclusters. The results demonstrated that the connection between obesity and T2D mainly relied on several pathways involved in the digestive metabolism, immunization, and signal transduction, such as adipocytokine, chemokine signaling pathway, T cell receptor signaling pathway, and MAPK signaling pathways. The relationships of almost all of these pathways with obesity and T2D have been verified by the previous reports individually. We also found that the different parts in the same pathway are activated in obesity and T2D. The association of cancer, obesity, and T2D was identified too here. As a conclusion, our network-based method not only gives better support for the close connection between obesity and T2D, but also provides a systemic view in understanding the molecular functions underneath the links. It should be helpful in the development of new therapies for obesity, T2D, and the associated diseases.

No MeSH data available.


Related in: MedlinePlus

The KEGG pathways enriched in obesity and T2D clusters. The enriched pathways of the obesity (orange ellipse) and T2D (blue ellipse) clusters are classified into three regulatory groups (metabolic, immune response, and signaling) and one disease-related group, which were highlighted by the colored triangles (purple, blue, red, and grass green). The size of ellipse represents the number of genes in the subclusters and the triangle size is proportional to the number of the links with obesity and T2D subclusters.
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fig4: The KEGG pathways enriched in obesity and T2D clusters. The enriched pathways of the obesity (orange ellipse) and T2D (blue ellipse) clusters are classified into three regulatory groups (metabolic, immune response, and signaling) and one disease-related group, which were highlighted by the colored triangles (purple, blue, red, and grass green). The size of ellipse represents the number of genes in the subclusters and the triangle size is proportional to the number of the links with obesity and T2D subclusters.

Mentions: As a result, there are 16 and 12 pathways significantly enriched in these obesity and T2D active clusters with or without the seed genes (Figure 4). It verified our conjecture very well as almost all these enriched pathways have been reported for their connection with the development of obesity and/or T2D, such as PPAR signaling pathway [9], insulin signaling pathway [37], and MAPK signaling pathway [38]. For instance, the PPAR signaling pathway is enriched in active cluster 2 of obesity, which has a vital function in adipocyte proliferation and differentiation in liver, muscle and adipose tissues [9]. The PPARs not only regulate lipid, carbohydrate, and amino acid metabolism, but also play an important role in systemic insulin sensitization through the combined effects of the production of adiponectin and reduction of lipotoxicity [9].


Network-Based Association Study of Obesity and Type 2 Diabetes with Gene Expression Profiles.

Zhang S, Wang B, Shi J, Li J - Biomed Res Int (2015)

The KEGG pathways enriched in obesity and T2D clusters. The enriched pathways of the obesity (orange ellipse) and T2D (blue ellipse) clusters are classified into three regulatory groups (metabolic, immune response, and signaling) and one disease-related group, which were highlighted by the colored triangles (purple, blue, red, and grass green). The size of ellipse represents the number of genes in the subclusters and the triangle size is proportional to the number of the links with obesity and T2D subclusters.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4530213&req=5

fig4: The KEGG pathways enriched in obesity and T2D clusters. The enriched pathways of the obesity (orange ellipse) and T2D (blue ellipse) clusters are classified into three regulatory groups (metabolic, immune response, and signaling) and one disease-related group, which were highlighted by the colored triangles (purple, blue, red, and grass green). The size of ellipse represents the number of genes in the subclusters and the triangle size is proportional to the number of the links with obesity and T2D subclusters.
Mentions: As a result, there are 16 and 12 pathways significantly enriched in these obesity and T2D active clusters with or without the seed genes (Figure 4). It verified our conjecture very well as almost all these enriched pathways have been reported for their connection with the development of obesity and/or T2D, such as PPAR signaling pathway [9], insulin signaling pathway [37], and MAPK signaling pathway [38]. For instance, the PPAR signaling pathway is enriched in active cluster 2 of obesity, which has a vital function in adipocyte proliferation and differentiation in liver, muscle and adipose tissues [9]. The PPARs not only regulate lipid, carbohydrate, and amino acid metabolism, but also play an important role in systemic insulin sensitization through the combined effects of the production of adiponectin and reduction of lipotoxicity [9].

Bottom Line: However, the molecular mechanisms of the disease relations are not well discovered yet.As a conclusion, our network-based method not only gives better support for the close connection between obesity and T2D, but also provides a systemic view in understanding the molecular functions underneath the links.It should be helpful in the development of new therapies for obesity, T2D, and the associated diseases.

View Article: PubMed Central - PubMed

Affiliation: Department of Bioinformatics & Biostatistics, School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

ABSTRACT
The increased prevalence of obesity and type 2 diabetes (T2D) has become an important factor affecting the health of the human. Obesity is commonly considered as a major risk factor for the development of T2D. However, the molecular mechanisms of the disease relations are not well discovered yet. In this study, the combination of multiple differential expression profiles and a comprehensive biological network of obesity and T2D allowed us to identify and compare the disease-responsive active modules and subclusters. The results demonstrated that the connection between obesity and T2D mainly relied on several pathways involved in the digestive metabolism, immunization, and signal transduction, such as adipocytokine, chemokine signaling pathway, T cell receptor signaling pathway, and MAPK signaling pathways. The relationships of almost all of these pathways with obesity and T2D have been verified by the previous reports individually. We also found that the different parts in the same pathway are activated in obesity and T2D. The association of cancer, obesity, and T2D was identified too here. As a conclusion, our network-based method not only gives better support for the close connection between obesity and T2D, but also provides a systemic view in understanding the molecular functions underneath the links. It should be helpful in the development of new therapies for obesity, T2D, and the associated diseases.

No MeSH data available.


Related in: MedlinePlus