CPEB4-Driven adipocyte reprogramming is required for adipogenesis and pathological inflammation

Abstract

Obesity is reaching pandemic dimensions and is an established instigator of many diseases, such as non alcoholic fatty liver disease, the most prevalent liver disease worldwide. Most studies in this regard have been focused on obesity-related disturbances taking place within the liver altough the implications of obesity on extrahepatic abdominal organs are of major relevance to get the whole picture of the disease. Here, we show that the RNA-binding protein CPEB4 is highly expressed in visceral fat during obesity and obesity associated liver disease, where it orchestrates a posttranscriptional reprogramming necessary for development and aggravation of diet-induced obesity. CPEB4 simultaneously regulates adipocyte differentiation and expansion, and the adipocyte-macrophage crosstalk. Consequently, CPEB4 depletion prevents the upregulation of adipocyte-related pathways and adipogenesis, and promotes an anti-inflammatory phenotype in visceral adipose tissue. These findings identify CPEB4 as an appealing therapeutic target for obesity.