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.

中文翻译：

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鉴定白色脂肪褐变中关键候选基因和分子途径：基于计算生物学的抗肥胖药发现。

背景技术肥胖症及其与肥胖症相关的代谢疾病的风险增加，已经成​​为富裕国家二十一世纪最大的公共卫生流行病之一。迄今为止，还没有治疗肥胖的理想药物。研究表明，激活棕色脂肪组织（BAT）可以促进能量消耗并抑制肥胖，这使得白色脂肪组织（WAT）的褐变成为肥胖症的潜在治疗靶标。我们的目标是通过使用公开可用的数据和计算工具，确定与WAT相关的基因和分子途径以及BAT活化为WAT褐变。这些知识可能有助于靶向治疗肥胖症和其他相关代谢疾病的相关信号通路。结果在这项研究中，我们使用文本挖掘来找出与棕色脂肪和白色脂肪褐变相关的基因。结合GeneCodis中的生物学过程和途径分析以及使用STRING和Cytoscape进行蛋白质-蛋白质相互作用分析，开发了高优先级目标基因列表。人类蛋白质图谱用于分析蛋白质表达。候选药物是根据最终基因的药物基因相互作用分析得出的。我们的研究确定了代表6种不同途径的18种基因，它们可能被33种药物作为可能的药物治疗方法。最终名单包括18种过氧化物酶体增殖物激活受体伽玛（PPAR-γ）激动剂，4种β3肾上腺素能受体（β3-AR）激动剂，1种胰岛素增敏剂，3种胰岛素，6种脂肪酶清除因子兴奋剂和其他药物。结论使用计算机文本挖掘，途径，