Identification of key candidate genes and molecular pathways in white fat browning: an anti-obesity drug discovery based on computational biology
Abstract Background Obesity—with its increased risk of obesity-associated metabolic diseases—has become one of the greatest public health epidemics of the twenty-first century in affluent countries. To date, there are no ideal drugs for treating obesity. Studies have shown that activation of brown a...
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| Format: | Article |
| Language: | English |
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BMC
2019-11-01
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| Series: | Human Genomics |
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| Online Access: | http://link.springer.com/article/10.1186/s40246-019-0239-x |
| _version_ | 1811262504840462336 |
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| author | Yuyan Pan Jiaqi Liu Fazhi Qi |
| author_facet | Yuyan Pan Jiaqi Liu Fazhi Qi |
| author_sort | Yuyan Pan |
| collection | DOAJ |
| description | Abstract Background Obesity—with its increased risk of obesity-associated metabolic diseases—has become one of the greatest public health epidemics of the twenty-first century in affluent countries. To date, there are no ideal drugs for treating obesity. Studies have shown that activation of brown adipose tissue (BAT) can promote energy consumption and inhibit obesity, which makes browning of white adipose tissue (WAT) a potential therapeutic target for obesity. Our objective was to identify genes and molecular pathways associated with WAT and the activation of BAT to WAT browning, by using publicly available data and computational tools; this knowledge might help in targeting relevant signaling pathways for treating obesity and other related metabolic diseases. Results In this study, we used text mining to find out genes related to brown fat and white fat browning. Combined with biological process and pathway analysis in GeneCodis and protein-protein interaction analysis by using STRING and Cytoscape, a list of high priority target genes was developed. The Human Protein Atlas was used to analyze protein expression. Candidate drugs were derived on the basis of the drug-gene interaction analysis of the final genes. Our study identified 18 genes representing 6 different pathways, targetable by a total of 33 drugs as possible drug treatments. The final list included 18 peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists, 4 beta 3 adrenoceptor (β3-AR) agonists, 1 insulin sensitizer, 3 insulins, 6 lipase clearing factor stimulants and other drugs. Conclusions Drug discovery using in silico text mining, pathway, and protein-protein interaction analysis tools may be a method of exploring drugs targeting the activation of brown fat or white fat browning, which provides a basis for the development of novel targeted therapies as potential treatments for obesity and related metabolic diseases. |
| first_indexed | 2024-04-12T19:26:42Z |
| format | Article |
| id | doaj.art-c8f8941800f346e8a95bc6f78abf2f09 |
| institution | Directory Open Access Journal |
| issn | 1479-7364 |
| language | English |
| last_indexed | 2024-04-12T19:26:42Z |
| publishDate | 2019-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Human Genomics |
| spelling | doaj.art-c8f8941800f346e8a95bc6f78abf2f092022-12-22T03:19:28ZengBMCHuman Genomics1479-73642019-11-0113111310.1186/s40246-019-0239-xIdentification of key candidate genes and molecular pathways in white fat browning: an anti-obesity drug discovery based on computational biologyYuyan Pan0Jiaqi Liu1Fazhi Qi2Department of Plastic and Reconstructive Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Plastic and Reconstructive Surgery, Zhongshan Hospital, Fudan UniversityDepartment of Plastic and Reconstructive Surgery, Zhongshan Hospital, Fudan UniversityAbstract Background Obesity—with its increased risk of obesity-associated metabolic diseases—has become one of the greatest public health epidemics of the twenty-first century in affluent countries. To date, there are no ideal drugs for treating obesity. Studies have shown that activation of brown adipose tissue (BAT) can promote energy consumption and inhibit obesity, which makes browning of white adipose tissue (WAT) a potential therapeutic target for obesity. Our objective was to identify genes and molecular pathways associated with WAT and the activation of BAT to WAT browning, by using publicly available data and computational tools; this knowledge might help in targeting relevant signaling pathways for treating obesity and other related metabolic diseases. Results In this study, we used text mining to find out genes related to brown fat and white fat browning. Combined with biological process and pathway analysis in GeneCodis and protein-protein interaction analysis by using STRING and Cytoscape, a list of high priority target genes was developed. The Human Protein Atlas was used to analyze protein expression. Candidate drugs were derived on the basis of the drug-gene interaction analysis of the final genes. Our study identified 18 genes representing 6 different pathways, targetable by a total of 33 drugs as possible drug treatments. The final list included 18 peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists, 4 beta 3 adrenoceptor (β3-AR) agonists, 1 insulin sensitizer, 3 insulins, 6 lipase clearing factor stimulants and other drugs. Conclusions Drug discovery using in silico text mining, pathway, and protein-protein interaction analysis tools may be a method of exploring drugs targeting the activation of brown fat or white fat browning, which provides a basis for the development of novel targeted therapies as potential treatments for obesity and related metabolic diseases.http://link.springer.com/article/10.1186/s40246-019-0239-xBrown fatBrowning of white fatPPAR-γβ3-ARText miningIn silico |
| spellingShingle | Yuyan Pan Jiaqi Liu Fazhi Qi Identification of key candidate genes and molecular pathways in white fat browning: an anti-obesity drug discovery based on computational biology Human Genomics Brown fat Browning of white fat PPAR-γ β3-AR Text mining In silico |
| title | Identification of key candidate genes and molecular pathways in white fat browning: an anti-obesity drug discovery based on computational biology |
| title_full | Identification of key candidate genes and molecular pathways in white fat browning: an anti-obesity drug discovery based on computational biology |
| title_fullStr | Identification of key candidate genes and molecular pathways in white fat browning: an anti-obesity drug discovery based on computational biology |
| title_full_unstemmed | Identification of key candidate genes and molecular pathways in white fat browning: an anti-obesity drug discovery based on computational biology |
| title_short | Identification of key candidate genes and molecular pathways in white fat browning: an anti-obesity drug discovery based on computational biology |
| title_sort | identification of key candidate genes and molecular pathways in white fat browning an anti obesity drug discovery based on computational biology |
| topic | Brown fat Browning of white fat PPAR-γ β3-AR Text mining In silico |
| url | http://link.springer.com/article/10.1186/s40246-019-0239-x |
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