| First Author | Yan C | Year | 2021 |
| Journal | Diabetes | Volume | 70 |
| Issue | 2 | Pages | 577-588 |
| PubMed ID | 33262120 | Mgi Jnum | J:306295 |
| Mgi Id | MGI:6712893 | Doi | 10.2337/db20-0146 |
| Citation | Yan C, et al. (2021) A High-Fat Diet Attenuates AMPK alpha1 in Adipocytes to Induce Exosome Shedding and Nonalcoholic Fatty Liver Development In Vivo. Diabetes 70(2):577-588 |
| abstractText | Exosomes are important for intercellular communication, but the role of exosomes in the communication between adipose tissue (AT) and the liver remains unknown. The aim of this study is to determine the contribution of AT-derived exosomes in nonalcoholic fatty liver disease (NAFLD). Exosome components, liver fat content, and liver function were monitored in AT in mice fed a high-fat diet (HFD) or treated with metformin or GW4869 and with AMPKalpha1-floxed (Prkaalpha1 (fl/fl)/wild-type [WT]), Prkaalpha1 (-/-), liver tissue-specific Prkaalpha1 (-/-), or AT-specific Prkaalpha1 (-/-) modification. In cultured adipocytes and white AT, the absence of AMPKalpha1 increased exosome release and exosomal proteins by elevating tumor susceptibility gene 101 (TSG101)-mediated exosome biogenesis. In adipocytes treated with palmitic acid, TSG101 facilitated scavenger receptor class B (CD36) sorting into exosomes. CD36-containing exosomes were then endocytosed by hepatocytes to induce lipid accumulation and inflammation. Consistently, an HFD induced more severe lipid accumulation and cell death in Prkaalpha1 (-/-) and AT-specific Prkaalpha1 (-/-) mice than in WT and liver-specific Prkaalpha1 (-/-) mice. AMPK activation by metformin reduced adipocyte-mediated exosome release and mitigated fatty liver development in WT and liver-specific Prkaalpha1 (-/-) mice. Moreover, administration of the exosome inhibitor GW4869 blocked exosome secretion and alleviated HFD-induced fatty livers in Prkaalpha1 (-/-) and adipocyte-specific Prkaalpha1 (-/-) mice. We conclude that HFD-mediated AMPKalpha1 inhibition promotes NAFLD by increasing numbers of AT CD36-containing exosomes. |
