Abstract
The promyelocytic leukemia protein is a well known tumor suppressor, but its role in metabolism is largely unknown. Mice with a deletion in the gene for PML (KO mice) exhibit altered gene expression in liver, adipose tissue, and skeletal muscle, an accelerated rate of fatty acid metabolism, abnormal glucose metabolism, constitutive AMP-activating kinase (AMPK) activation, and insulin resistance in skeletal muscle. Last, an increased rate of energy expenditure protects PML KO mice from the effects of obesity induced by a Western diet. Collectively, our study uncovers a previously unappreciated role of PML in the regulation of metabolism and energy balance in mice.
Highlights
The role of promyelocytic leukemia (PML) in metabolism remains largely unexplored
Loss of PML Re-patterns Gene Expression in Metabolic Tissues—Our previous microarray analysis [16] indicated that deleting the gene for PML altered an array of genes involved in lipid/fatty acid and cholesterol metabolism in primary human endothelial cells, implying that PML has a role in metabolic regulation
To further characterize the function of PML gene on metabolism, we analyzed the pattern of mRNA accumulation for genes related to energy metabolism in liver, epididymal white adipose tissue (eWAT), brown adipose tissue (BAT), and skeletal muscles in wild-type (WT) control and PML KO animals that had been fasted overnight
Summary
Results: PML ablation re-patterns energy balance in mice by promoting fatty acid metabolism. The promyelocytic leukemia protein is a well known tumor suppressor, but its role in metabolism is largely unknown. Previous studies that bridge cancer genetics and metabolism have revealed an important role for tumor suppressors, such as LKB1 (serine/threonine kinase 11) [3], in directly regulating metabolism. Several recent studies reported that the well known tumor suppressor promyelocytic leukemia (PML) plays a regulatory role in metabolism by controlling peroxisome proliferator-activated receptor. The physiological role of PML remains largely unknown, our previous microarray analyses indicate that knockdown of PML re-patterns an array of genes involved in lipid and fatty acid metabolism in endothelial cells [16], suggesting a role for PML in the control of metabolism. We identified a novel role of PML in metabolic control that has not previously been reported
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