Panel A shows a dot plot of M Y C T 1 gene expression in various human tissues, highlighting its specificity to endothelial lineages. Panel B displays chromogenic immunostaining of M Y C T 1 protein in human tissues and tumors, with arrows indicating M Y C T 1 signals. Panel C outlines the experimental workflow for monitoring M y c t 1 e c K O mice phenotype. Panel D presents a line graph showing reduced body weight in M y c t 1 e c K O mice compared to wildtype. Panel E includes whole-body C T scans of wildtype and Myct1ecKO mice, highlighting differences in fat distribution. Panel F quantifies the volume of inguinal W A T (i W A T) and interscapular B A T (i B A T) tissue from C T scans. Panel G shows macroscopic images of fat pads from wildtype and M y c t 1 e c K O mice. Panel H quantifies the fat pad weight to body weight ratio. Panel I displays H and E staining of retroperitoneal fat sections, showing reduced adipocyte size in M y c t 1 e c K O mice. Panel J quantifies adipocyte size relative to wildtype. Panel K outlines the experimental workflow for a high-fat diet experiment. Panel L shows a line graph of body weight change in wildtype and M y c t 1 e c K O mice under different diets. Panel M illustrates the effect of M y c t 1 ablation on white adipose tissue expansion.
Pan-endothelial MYCT1 is required for WAT expansion. (A) MYCT1 gene expression is specific to the endothelial lineages. Dot plot representation of MYCT1 expression in blood and lymphatic endothelial and mural cells across various human tissues. Dataset by Barnett et al. (2024). (B) MYCT1 protein expression is endothelial-specific across human tissues and tumors. Chromogenic immunostaining of MYCT1 (brown) in human intestine, skin, white fat, and in small cell lung cancer. A, artery; V, vein; C, capillary; L, lymphatic vessel. Arrows, MYCT1 signal. Scale bar, 50 μm. (C) Experimental workflow for long term monitoring of Myct1ecKO mice phenotype. (D) Adult Myct1ecKO mice display reduced body weight. n = 10 female mice per genotype; mean ± SD; multiple unpaired t tests, P = 0.0045 (*). (E)Myct1 ablation reduces size of visceral and s.c. WAT. Whole-body CT-scans of wild-type and Myct1ecKO mice. Is, interscapular fat; Mes, mesenteric fat; Gon, gonadal fat; Ing, inguinal fat. (F) Quantification of interscapular WAT (IsWAT) and BAT (IsBAT) tissue volume from CT scans. BAT, brown adipose tissue. n = 5 mice per genotype; mean ± SD; two-way ANOVA with Sidak’s multiple comparisons test; P < 0.0001 (*) for IsWAT and P > 0.05 for IsBAT. (G) Macroscopic images of interscapular, retroperitoneal, and gonadal fat pads of wild-type and Myct1ecKO mice. Scale bar, 5 mm. (H) Quantification of fat pad weight to body weight ratio relative to wild-type mice. n = 6–7 mice per genotype; mean ± SD; multiple Welch’s t tests, P = 0.0072 (*) for IsWAT, P > 0.05 for IsBAT, P = 0.018 (*) for Ing (inguinal), P = 0.032 (*) for RP (retroperitoneal), P = 0.015 (*) for Gon (gonadal), and P = 0.037 (*) for Mes (mesenteric). (I)Myct1 ablation reduces the size of adipocytes. H&E staining of retroperitoneal fat sections of wild-type and Myct1ecKO mice. Scale bar, 50 μm. (J) Quantification of adipocyte size relative to wild-type. n = 6 mice per genotype; mean ± SD; unpaired t test, P = 0.033 (*). (K) Experimental workflow for HFD experiment. (L) HFD accelerates differences in body weight change between wild-type and Myct1ecKO mice. n = 5 mice per diet and genotype; mean ± SD; two-way ANOVA with Tukey’s multiple comparisons test, P = 0.023 (*) for HFD and P > 0.05 for standard control diet (SD). (M)Myct1 ablation limits WAT (yellow, adipocytes) expansion. Icons used in A, C, K, and M were created with BioRender.com and modified in Affinity. See also Fig. S1.