| First Author | Yang X | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 627 |
| PubMed ID | 38245529 | Mgi Jnum | J:346035 |
| Mgi Id | MGI:7578354 | Doi | 10.1038/s41467-024-44924-w |
| Citation | Yang X, et al. (2024) Leukemia inhibitory factor suppresses hepatic de novo lipogenesis and induces cachexia in mice. Nat Commun 15(1):627 |
| abstractText | Cancer cachexia is a systemic metabolic syndrome characterized by involuntary weight loss, and muscle and adipose tissue wasting. Mechanisms underlying cachexia remain poorly understood. Leukemia inhibitory factor (LIF), a multi-functional cytokine, has been suggested as a cachexia-inducing factor. In a transgenic mouse model with conditional LIF expression, systemic elevation of LIF induces cachexia. LIF overexpression decreases de novo lipogenesis and disrupts lipid homeostasis in the liver. Liver-specific LIF receptor knockout attenuates LIF-induced cachexia, suggesting that LIF-induced functional changes in the liver contribute to cachexia. Mechanistically, LIF overexpression activates STAT3 to downregulate PPARalpha, a master regulator of lipid metabolism, leading to the downregulation of a group of PPARalpha target genes involved in lipogenesis and decreased lipogenesis in the liver. Activating PPARalpha by fenofibrate, a PPARalpha agonist, restores lipid homeostasis in the liver and inhibits LIF-induced cachexia. These results provide valuable insights into cachexia, which may help develop strategies to treat cancer cachexia. |
