Title

Dynamic Reversal of Insulin Sensitivity during Adipogenesis by the Timing and Order of CEBPB and CEBPA Levels

ORCiD

Atefeh Rabiee: 0000-0003-4060-7328

Document Type

Poster

Conference Title/Conference Publication

Research Symposium: 4th Annual Frontiers in Diabetes

Location

Stanford, CA

Conference Dates

April 24, 2019

Date of Presentation

4-24-2015

Abstract

Dysfunctional adipose tissue is a hallmark of insulin resistance (IR), a disease that is highly correlated with diabetes and cardiovascular disease. The development of healthy functioning adipocytes (fat cells) requires that, early in adipogenesis, the expression of the transcription factor C/EBPβ increases, resulting in an upregulation in the expression of its downstream target PPARγ, the master regulator of adipogenesis. Under normal conditions, C/EBPβ expression subsequently decreases as adipogenesis progresses. However, under inflammatory (IR) conditions, expression of C/EBPβ remains high, and reports suggest that this high C/EBPβ contributes to the inflammatory state. Understanding how C/EBPβ switches from being adipogenic (promoting insulin sensitivity) to inflammatory (promoting IR) could be a promising new way to treat IR, but the mechanisms underlying this switch are poorly understood. Here, we present evidence that high C/EBPβ in adipocytes under inflammatory conditions leads to IR by blocking access of C/EBP onto the promoters of adipogenic genes. Here we show that the timing of expression of C/EBPβ and C/EBP needs to be precisely controlled for adipogenesis to correctly progress and disruption of this timing leads to IR.

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