Fig 1: VAT-directed FGF21 gene therapy reduces ATM inflammation in DIO mice(A) Representative FACS plot of ATMs in gWAT. (B) ATMs as a percentage of all CD45+ cells. (C) Percentage of CD11c+, CD206- ATMs. (D) Percentage of CD11c-, CD206+ ATMs. (E) Percentage of CD11c+, CD206+ ATMs. (F) Percentage of natural killer T cells. (G) Percentage of CD3+ cells. (H) Percentage of CD4+ T cells. (I) Percentage of CD8+ T cells. Data are means ± SEM. Sample size (B–E), Rec2-Empty, n = 5; Rec2-FGF21, n = 7. Sample size (F–I), Rec2-Empty, n = 6; Rec2-FGF21, n = 7. +p < 0.06, *p < 0.05, **p < 0.01, ***p < 0.001.
Fig 2: VAT-directed FGF21 gene therapy alters adipose gene expression in DIO mice(A) Gene expression profile of gWAT. (B) Gene expression profile of rWAT. (C) Gene expression profile of iWAT. (D) Gene expression profile of BAT (n = 5, Rec2-Empty; n = 7, Rec2-FGF21 for Ppargc1a, Dio2, Ppara only). Data are means ± SEM. Sample size, Rec2-Empty, n = 7; Rec2-FGF21, n = 7 unless otherwise noted. +p < 0.06, *p < 0.05, **p < 0.01, ***p < 0.001.
Fig 3: Gross tissues and liver analysis(A) Tissue weights at sacrifice. (B) Relative tissue weights at sacrifice. (C) Liver weight at sacrifice. (D) Relative liver weight at sacrifice. (E) Representative H&E staining of liver tissue. Scale bar, 50 µm. (F) Hepatic triglycerides. (G) Gene expression profiling of liver tissue. Data are means ± SEM. Sample size, Rec2-Empty, n = 7; Rec2-FGF21, n = 7. +p < 0.06, *p < 0.05, **p < 0.01, ***p < 0.001.
Fig 4: VAT-directed Rec2-FGF21 gene therapy under NCD conditions(A) Vector schematic for Rec2-Empty and Rec2-FGF21. (B) Experimental timeline. (C) Body weights following rAAV administration. (D) Relative daily food intake. (E) Relative fat mass at 21 weeks post-rAAV-injection. (F) Relative lean mass at 21 weeks post-rAAV-injection. (G) Glucose tolerance test at 5 weeks post-rAAV-injection. (H) Glucose tolerance test area under the curve. (I) Insulin tolerance test at 20 weeks post-rAAV-injection. (J) Insulin tolerance test area under the curve. (K) Relative tissue weight at sacrifice. (L) Serum FGF21 at sacrifice. (M) Serum leptin at sacrifice. (N) Serum CCL2 at sacrifice (n = 4, Rec2-Empty; n = 7, Rec2-FGF21). (O) Gene expression profile of gWAT (n = 4, Rec2-Empty; n = 6, Rec2-FGF21). Data are means ± SEM. Sample size, Rec2-Empty, n = 4; Rec2-FGF21, n = 8 unless otherwise noted. +p < 0.06, *p < 0.05, **p < 0.01, ***p < 0.001.
Fig 5: VAT-directed Rec2-FGF21 gene therapy in DIO mice(A) Experimental timeline. (B) Body weights. (C) Percent change in body weight. (D) Relative daily food intake. (E) Relative fat mass at 16 weeks post-rAAV-injection. (F) Relative lean mass at 16 weeks post-rAAV-injection. (G) Insulin tolerance test at 8 weeks post-rAAV-injection (n = 7, Rec2-Empty; n = 6, Rec2-FGF21). (H) Insulin tolerance test area under the curve (n = 7, Rec2-Empty; n = 6, Rec2-FGF21). (I) Glucose tolerance test at 10 weeks post-rAAV-injection. (J) Glucose tolerance test area under the curve. Data are means ± SEM. Sample size, Rec2-Empty, n = 7; Rec2-FGF21, n = 7 unless otherwise noted. +p < 0.06, *p < 0.05, **p < 0.01, ***p < 0.001.
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