Analysis of in vitro insulin resistance models and their physiological relevance to in vivo diet-induced adipose insulin resistance

摘要

Diet-induced obesity predisposes individuals to insulin resistance, and adipose tissue has a major role in the disease. Insulin resistance can be induced in cultured adipocytes by a variety of treatments, but it is unknown what aspects of the in vivo responses are captured by these models. We use global RNA-sequencing (RNA-Seq) to investigate changes induced by TNFα, hypoxia, dexamethasone, high insulin, and a combination of TNFα and hypoxia, comparing the results to the changes in white adipose tissue from diet-induced obese (DIO) mice. We found that different in vitro models capture distinct features of DIO adipose insulin resistance, and a combined treatment of TNFα and hypoxia is most able to mimic the in vivo changes. Using genome-wide DNase I hypersensitivity followed by sequencing (DNase-Seq), we further examined the transcriptional regulation of TNFα-induced insulin resistance, and we found that C/EPBβ is a potential key regulator of adipose insulin resistance.