Pluto Bioinformatics

GSE137678: STAT5 is required for lipid breakdown and beta-adrenergic responsiveness of brown adipose tissue

Bulk RNA sequencing

Increasing energy expenditure through activation of brown adipose tissue (BAT) thermogenesis is an attractive approach to counteract obesity. Thus, it is essential to understand molecular mechanisms that control BAT functions. Here, we describe signal transducer and activator of transcription (STAT) 5 as key regulator of BAT functionality. We found that STAT5 is necessary for acute cold-induced temperature maintenance and stimulated lipid breakdown in BAT using mice that harbour an adipocyte-specific deletion of Stat5a/b genes. In addition, the mitochondrial respiratory capacity of primary differentiated brown adipocytes from STAT5 deficient mice was diminished. We show that increased sensitivity to cold stress upon STAT5 deficiency was associated with reduced expression of thermogenic key player uncoupling protein 1, while decreased stimulated lipolysis of STAT5-deficient BAT explants was linked to decreased protein kinase A activity. In addition, brown remodeling of white fat was diminished following chronic -adrenergic stimulation. This impairment was linked to a decrease in mitochondrial functionality. We conclude that STAT5 is essential for the -adrenergic responsiveness of brown adipose tissue and the physiologic function of thermogenic adipose tissue. SOURCE: Frank Ruge ( - Moriggl University of Veterinary Medicine

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