Identification of key candidate genes and molecular pathways in white fat browning: an anti-obesity drug discovery based on computational biology

Yuyan Pan,Jiaqi Liu,Fazhi Qi

doi:10.1186/s40246-019-0239-x

Abstract

BackgroundObesity—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.ResultsIn 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.ConclusionsDrug 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.

Highlights

Obesity is a global public health issue [1]
Biological process, and pathway analysis According to the data mining strategy described in Fig. 1, in the text mining process, 380 genes were found related to brown-fat-like development, brown fat, and brown adipose tissue (BAT) and 131 genes were common to all the three lists (Fig. 2)
The GO biological process annotations performed in GeneCodis showed that the most highly enriched terms were closely related to the brown-fat-like pathology

Summary

Introduction

Obesity is a global public health issue [1]. Excessive consumption of energy and the lack of exercise have increased the prevalence of obesity throughout the world. Based on the US population, 35% of adult men and 37% of adult women are obese [2] This dramatically increases the risk of obesity-associated metabolic diseases, such as hyperglycemia, insulin resistance, type 2. 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. 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

Objectives

Methods

Results

Discussion

Conclusion