| First Author | Han L | Year | 2023 |
| Journal | Nat Cell Biol | Volume | 25 |
| Issue | 7 | Pages | 1033-1046 |
| PubMed ID | 37264180 | Mgi Jnum | J:355690 |
| Mgi Id | MGI:7520974 | Doi | 10.1038/s41556-023-01162-4 |
| Citation | Han L, et al. (2023) Lipid droplet-associated lncRNA LIPTER preserves cardiac lipid metabolism. Nat Cell Biol 25(7):1033-1046 |
| abstractText | Lipid droplets (LDs) are cellular organelles critical for lipid homeostasis, with intramyocyte LD accumulation implicated in metabolic disorder-associated heart diseases. Here we identify a human long non-coding RNA, Lipid-Droplet Transporter (LIPTER), essential for LD transport in human cardiomyocytes. LIPTER binds phosphatidic acid and phosphatidylinositol 4-phosphate on LD surface membranes and the MYH10 protein, connecting LDs to the MYH10-ACTIN cytoskeleton and facilitating LD transport. LIPTER and MYH10 deficiencies impair LD trafficking, mitochondrial function and survival of human induced pluripotent stem cell-derived cardiomyocytes. Conditional Myh10 deletion in mouse cardiomyocytes leads to LD accumulation, reduced fatty acid oxidation and compromised cardiac function. We identify NKX2.5 as the primary regulator of cardiomyocyte-specific LIPTER transcription. Notably, LIPTER transgenic expression mitigates cardiac lipotoxicity, preserves cardiac function and alleviates cardiomyopathies in high-fat-diet-fed and Lepr(db/db) mice. Our findings unveil a molecular connector role of LIPTER in intramyocyte LD transport, crucial for lipid metabolism of the human heart, and hold significant clinical implications for treating metabolic syndrome-associated heart diseases. |
