Fig. 7: LIPTER transgene mitigates cardiomyopathies and cardiac dysfunctions in HFD-fed and Leprdb/db mice.
From: Lipid droplet-associated lncRNA LIPTER preserves cardiac lipid metabolism
a, Scheme of CM lipotoxicity assay with 400 μM palmitic acid treatment on hiPSC-CMs for 4 days. b,c, Cleaved caspase3+ CM ratios (b) and TUNEL+ CM ratios (c) in control and LIPTEROE hiPSC-CMs after PA treatment (b,c, n = 3 independent experiments). d, Schematic of investigating LIPTER(Tg) effects on cardiac abnormalities in HFD‐fed mice. e, Oil Red O and haematoxylin staining of mouse hearts after 7 month HFD feeding. f,g, FA (f, n = 5 mice each group) and TAG (g, n = 7 mice each group) concentrations were next measured. h, FAO rates of whole WT and LIPTER(Tg) mouse hearts at 3 months of age (n = 5 mice each group). i, GO biological processes significantly enriched in the upregulated genes in LIPTER (Tg) versus WT mouse hearts. j, Picrosirius Red and Fast Green co-staining of mouse hearts after 10 month HFD feeding. k, Quantification of relative red fibrotic areas in whole hearts (n = 3 mice each group). l,m, EF (l) and FS (m) measurements of WT and LIPTER(Tg) mice fed on HFD or NC for 10 months. n = 5 mice (WT + NC), n = 6 mice (WT + HFD), n = 7 mice (Tg + HFD). n, RIP-seq reads plot showing LIPTER pulldown by anti-Myh10 antibody in LIPTER (Tg) mouse heart. Red arrow indicates the reads enrichment on LIPTER exon 3. The experiment was carried out in two mice, each genotype with similar outcomes. o, A scheme for delivering LIPTER and controls (GFP, AS-LIPTER) into Leprdb/db mouse CMs using AAV9 virus. p, RT–qPCR detecting LIPTER expressions in Leprdb/db mouse hearts 6 weeks post AAV9 injection (n = 5 mice per group, except n = 4 mice in the GFP group). q, Oil Red O staining of Leprdb/db mouse hearts 6 weeks post AAV9 injection. r, FAO rates of Leprdb/db mouse hearts 6 weeks post AAV9 injection (n = 5 mice per group, except n = 4 mice in the No AAV group). s, CM size analysis using WGA staining 6 weeks post AAV9 injection (n = 5 mice per group, except n = 4 mice in the GFP group). t,u, EF (t) and FS (u) measurements in WT and Leprdb/db mice 6 weeks post AAV9 injection (n = 5 mice per group, except n = 4 mice in the GFP group). In b, c, f–h, k–m, p and r–u, bars are presented as mean ± s.e.m. Unpaired two-tailed t-test is used for comparison. Source numerical data are available in source data.
