| First Author | Wang H | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 33320092 | Mgi Jnum | J:325524 |
| Mgi Id | MGI:6714594 | Doi | 10.7554/eLife.63665 |
| Citation | Wang H, et al. (2020) An AMPK-dependent, non-canonical p53 pathway plays a key role in adipocyte metabolic reprogramming. Elife 9:e63665 |
| abstractText | 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. |
