| First Author | An YA | Year | 2019 |
| Journal | Nat Metab | Volume | 1 |
| Issue | 12 | Pages | 1243-1257 |
| PubMed ID | 31984308 | Mgi Jnum | J:301133 |
| Mgi Id | MGI:6502894 | Doi | 10.1038/s42255-019-0149-1 |
| Citation | An YA, et al. (2019) Dysregulation of Amyloid Precursor Protein Impairs Adipose Tissue Mitochondrial Function and Promotes Obesity. Nat Metab 1(12):1243-1257 |
| abstractText | Mitochondrial function in white adipose tissue (WAT) is an important yet understudied aspect in adipocyte biology. Here, we report a role for amyloid precursor protein (APP) in compromising WAT mitochondrial function through a high-fat diet (HFD)-induced, unconventional mis-localization to mitochondria that further promotes obesity. In humans and mice, obese conditions significantly induce APP production in WAT and its enrichment in mitochondria. Mechanistically, a HFD-induced dysregulation of signal recognition particle subunit 54c is responsible for the mis-targeting of APP to adipocyte mitochondria. Mis-localized APP blocks the protein import machinery, leading to mitochondrial dysfunction in WAT. Adipocyte-specific and mitochondria-targeted APP overexpressing mice display increased body mass and reduced insulin sensitivity, along with dysfunctional WAT due to a dramatic hypertrophic program in adipocytes. Elimination of adipocyte APP rescues HFD-impaired mitochondrial function with significant protection from weight gain and systemic metabolic deficiency. Our data highlights an important role of APP in modulating WAT mitochondrial function and obesity-associated metabolic dysfunction. |
