Gene expression signature of brown and inguinal white fat of mice kept at 30°C vs. 5°C

Activation and recruitment of thermogenic cells in human white adipose tissues (“browning”) can counteract obesity and associated metabolic disorders. However, quantifying the effects of therapeutic interventions on browning remains enigmatic. Here, we devise a computational approach, profiling of fat tissue types (ProFAT), for the quantification of thermogenic potential of heterogeneous fat biopsies based on the prediction of white and brown adipocytes content from raw gene expression profiles. ProFat systematically integrates 103 mouse fat-derived transcriptomes to identify unbiased and robust gene signatures of brown and white adipocytes. Application of ProFAT to 80 mouse and 97 human transcriptional profiles from 14 independent studies correctly predicts browning capacity upon various physiological and pharmacological stimuli. Our study represents the most exhaustive comparative analysis of public data on adipose biology towards quantification of browning after personalized medical intervention. ProFat is freely available and should become increasingly powerful with the growing wealth of transcriptomics data. The experiment was performed with female, 16 weeks old WT mice. All mice were bred, born and weaned at 30°C. At the age of 10-12 weeks, half of the mice were transferred to a temperature-controlled (+/- 0.5°C) climate chamber and kept for two weeks at 18°C followed by 3 weeks at 5°C. Afterwards, mice kept at 30°C and 5°C were euthanized after 2-3 hours food withdrawal, and serum and tissue samples were collected.