Han, LeiHuang, DayangWu, ShiyongLiu, ShengWang, ChengSheng, YiLu, XiongbinBroxmeyer, Hal E.Wan, JunYang, Lei2024-02-132024-02-132023Han L, Huang D, Wu S, et al. Lipid droplet-associated lncRNA LIPTER preserves cardiac lipid metabolism. Nat Cell Biol. 2023;25(7):1033-1046. doi:10.1038/s41556-023-01162-4https://hdl.handle.net/1805/38412Lipid 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 Leprdb/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.en-USAttribution 4.0 InternationalLong non-coding RNAsCardiomyopathiesOrganellesArticle