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使用哺乳动物基因表达谱鉴定潜在的热量限制模拟物。

Identification of putative calorie restriction mimetics using mammalian gene expression profiles.

机构信息

Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow, G61 1BD, UK.

Institute of Cancer Sciences, University of Glasgow, Glasgow, UK.

出版信息

Open Biol. 2020 Sep;10(9):200158. doi: 10.1098/rsob.200158. Epub 2020 Sep 16.

DOI:10.1098/rsob.200158
PMID:32931724
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7536090/
Abstract

Obesity is a risk factor for cardiovascular diseases, diabetes and cancer. In theory, the obesity problem could be solved by the adherence to a calorie-restricted diet, but that is not generally achieved in practice. An alternative is a pharmacological approach, using compounds that trigger the same metabolic changes associated with calorie restriction. Here, I expand in the pharmacological direction by identifying compounds that induce liver gene signature profiles that mimic those induced by calorie restriction. Using gene expression profiles from mice and rat, I identify corticosteroids, PPAR agonists and some antibacterial/antifungal as candidate compounds mimicking the response to calorie restriction in the liver gene signatures.

摘要

肥胖是心血管疾病、糖尿病和癌症的一个风险因素。从理论上讲，通过遵循热量限制饮食可以解决肥胖问题，但在实践中通常无法实现。另一种方法是采用药理学方法，使用能引发与热量限制相关的相同代谢变化的化合物。在这里，我通过确定能诱导肝脏基因特征谱的化合物来扩展药理学方向，这些特征谱模拟了热量限制所诱导的特征谱。我使用来自小鼠和大鼠的基因表达谱，确定了皮质类固醇、PPAR 激动剂和一些抗菌/抗真菌化合物作为模拟肝脏基因特征对热量限制反应的候选化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fac/7536090/c9252c7d8c04/rsob-10-200158-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fac/7536090/6906d022c29e/rsob-10-200158-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fac/7536090/821c0e3bbccb/rsob-10-200158-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fac/7536090/c9252c7d8c04/rsob-10-200158-g3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fac/7536090/6906d022c29e/rsob-10-200158-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fac/7536090/821c0e3bbccb/rsob-10-200158-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0fac/7536090/c9252c7d8c04/rsob-10-200158-g3.jpg

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Modern pharmacological treatment of obese patients.肥胖患者的现代药物治疗。
Ther Adv Endocrinol Metab. 2020 Jan 22;11:2042018819897527. doi: 10.1177/2042018819897527. eCollection 2020.
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mTORC1 amplifies the ATF4-dependent de novo serine-glycine pathway to supply glycine during TGF-β-induced collagen biosynthesis.mTORC1 扩增 ATF4 依赖性从头丝氨酸-甘氨酸途径，以在 TGF-β 诱导的胶原生物合成期间提供甘氨酸。
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药物重定位：进展、挑战和建议。
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A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles.下一代连接图谱：L1000平台及首批100万个图谱
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Identification of tissue-specific transcriptional markers of caloric restriction in the mouse and their use to evaluate caloric restriction mimetics.小鼠中热量限制的组织特异性转录标志物的鉴定及其在评估热量限制模拟物中的应用。
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Chronic Activation of Hepatic Nrf2 Has No Major Effect on Fatty Acid and Glucose Metabolism in Adult Mice.肝脏Nrf2的慢性激活对成年小鼠的脂肪酸和葡萄糖代谢没有重大影响。
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Pharmacological Approaches in the Treatment and Maintenance of Weight Loss.药物治疗在减肥治疗和维持中的应用。
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The Molecular Signatures Database (MSigDB) hallmark gene set collection.分子特征数据库（MSigDB）标志性基因集集合。
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