Diet-induced obesity predisposes individuals to insulin resistance, and adipose tissue has a major role in the etiology of disease.  Adipose insulin resistance can be induced in cultured adipocytes by a variety of treatments, but it is unknown what aspects of in vivo adipose insulin resistance are captured by these models.  We use global RNA-sequencing (RNA-Seq) to investigate gene expression changes induced by treatments with TNF, hypoxia, dexamethasone, and high insulin, comparing the results to data of white adipose tissue from diet-induced obese (DIO) mice.  While no in vitro model could faithfully mimic all the transcriptional changes occurring in DIO mouse adipose tissue, both TNF and hypoxia treatments capture the downregulation of various metabolic pathways.  Using genome-wide DNase I hypersensitivity followed by sequencing (DNase-Seq ), we further examined the transcriptional regulation of TNF-induced insulin resistance.  We conclude that different in vitro models capture different features of DIO adipose insulin resistance. SOURCE: Kinyui Alice LO (lky@mit.edu) - Fraenkel MIT

Pluto Bioinformatics

GSE35724: Comprehensive analysis of four in vitro insulin resistance models