An AMPK-dependent, non-canonical p53 pathway plays a key role in adipocyte metabolic reprogramming
- Boston University, United States
- Massachusetts General Hospital Cancer Center and Harvard Medical School, United States
- Icahn School of Medicine at Mount Sinai, United States
Abstract
It has been known adipocytes increase p53 expression and activity in obesity, however, only canonical p53 functions (i.e., senescence and apoptosis) are attributed to inflammation-associated metabolic phenotypes. Whether or not p53 is directly involved in mature adipocyte metabolic regulation remains unclear. Here we show p53 protein expression can be up-regulated in adipocytes by nutrient starvation without activating cell senescence, apoptosis, or a death-related p53 canonical pathway. Inducing the loss of p53 in mature adipocytes significantly reprograms energy metabolism and this effect is primarily mediated through a AMP-activated protein kinase (AMPK) pathway and a novel downstream transcriptional target, lysosomal acid lipase (LAL). The pathophysiological relevance is further demonstrated in a conditional and adipocyte-specific p53 knockout mouse model. Overall, these data support a non-canonical p53 function in the regulation of adipocyte energy homeostasis and indicate that the dysregulation of this pathway may be involved in developing metabolic dysfunction in obesity.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for figures.
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Funding
National Institute of Diabetes and Digestive and Kidney Diseases (DK-112945)
- Libin Liu
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal studies were performed in accordance with the guidelines and under approval of the Institutional Review Committee for the Animal Care and Use of Boston University. (Protocol #201800404).
Copyright
© 2020, Wang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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An AMPK-dependent, non-canonical p53 pathway plays a key role in adipocyte metabolic reprogramming
eLife 9:e63665.
https://doi.org/10.7554/eLife.63665
