An AMPK-dependent, non-canonical p53 pathway plays a key role in adipocyte metabolic reprogramming
- Boston University, 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.
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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
