Discovering compounds mimicking calorie restriction using mammalian gene expression profiles

Abstract

Obesity is a risk factor for cardiovascular diseases, diabetes and cancer. In theory the obesity problem could be solve 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. Liver gene signature analysis can be used to identify compounds that mimic calorie restriction.

Dietary and pharmacological induction of serine synthesis genes

“…I have previously introduced a gene expression analysis to identify candidate compounds inducing a specified gene signature in a specified tissue 8 . For sake of selfconsistency, I transcribe sections of that methodology here.…”

“…To identify compounds that induce the serine synthesis from 3-phosphoglycerate I took advantage of a toxicology study reporting the gene expression profiles of rats exposed to different compounds, including several drugs currently in use to treat a variety of illnesses 16 . I have previously shown that this resource can be used to identify compounds that mimic calorie restriction 8 . Here I will use the same approach to identify compounds that induces serine synthesis.…”