| First Author | Lu D | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 4214 |
| PubMed ID | 38760332 | Mgi Jnum | J:357379 |
| Mgi Id | MGI:7642508 | Doi | 10.1038/s41467-024-48471-2 |
| Citation | Lu D, et al. (2024) Liver ACOX1 regulates levels of circulating lipids that promote metabolic health through adipose remodeling. Nat Commun 15(1):4214 |
| abstractText | The liver gene expression of the peroxisomal beta-oxidation enzyme acyl-coenzyme A oxidase 1 (ACOX1), which catabolizes very long chain fatty acids (VLCFA), increases in the context of obesity, but how this pathway impacts systemic energy metabolism remains unknown. Here, we show that hepatic ACOX1-mediated beta-oxidation regulates inter-organ communication involved in metabolic homeostasis. Liver-specific knockout of Acox1 (Acox1-LKO) protects mice from diet-induced obesity, adipose tissue inflammation, and systemic insulin resistance. Serum from Acox1-LKO mice promotes browning in cultured white adipocytes. Global serum lipidomics show increased circulating levels of several species of omega-3 VLCFAs (C24-C28) with previously uncharacterized physiological role that promote browning, mitochondrial biogenesis and Glut4 translocation through activation of the lipid sensor GPR120 in adipocytes. This work identifies hepatic peroxisomal beta-oxidation as an important regulator of metabolic homeostasis and suggests that manipulation of ACOX1 or its substrates may treat obesity-associated metabolic disorders. |
