Fig. 5: C1632 attenuates hepatosteatosis in a genetic mouse model of NAFLD. | Nature Communications

Fig. 5: C1632 attenuates hepatosteatosis in a genetic mouse model of NAFLD.

From: Pharmacological inhibition of Lin28 promotes ketogenesis and restores lipid homeostasis in models of non-alcoholic fatty liver disease

Fig. 5: C1632 attenuates hepatosteatosis in a genetic mouse model of NAFLD.The alternative text for this image may have been generated using AI.

a, b Representative immunoblot analysis and quantitative densitometric analyses for Lin28A, Lin28B and NCoR1 in livers from 28-week-old Pten-/- male mice treated with vehicle or C1632 (50 mg/kg) after 6 weeks of treatment (3 IP injections per week). α-Tubulin was used as a loading control (n = 3 mice/group; Lin28A ***P = 0.0002; Lin28B, *P = 0.0183; NCoR1, *P = 0.0172). c, d Relative mRNA levels of lipogenic and ketogenic genes in livers from Pten-/- male mice treated with vehicle or C1632 as described in (a) (n = 4 mice/group; Acl, ***P = 0.0003; Acs, **P = 0.0076; Scd1, **P = 0.0074; Cpt1a, *P = 0.0181; Hmgcs2, ***P = 0.0005; Hmgcl, *P = 0.0280; Fgf21, *P = 0.0450). β-Actin was used as a housekeeping gene. e Serum β-OHB levels in Pten-/-mice treated with vehicle or C1632 as described in (a) (n = 4 mice/group, *P = 0.0331). f Relative mRNA levels of inflammation and fibrosis markers in livers from Pten-/- male mice treated with vehicle or C1632 as described in (a) (n = 4 mice/group; TNFα, *P = 0.0424; IL1β, *P = 0.0183; Ccl2, *P = 0.0119; Cxcl10, *P = 0.0157; Col1a1, *P = 0.0409; Timp1 *P = 0.0356, TGFb, *P = 0.0298). β-Actin was used as a housekeeping gene. g Representative Hematoxylin and Eosin (H&E) staining and Perilipin (PLIN2) staining of liver sections from vehicle and C1632 (50 mg/kg)-treated 28-week old Pten-/- mice after 6 weeks of treatment (3 IP injections per week). Liver tissues were collected 2 h after the last C1632 injection. Scale bars correspond to 300 μm. h–j Lipid droplet size and number were quantified by Image J (n = 17-21 histological images/group, ****P < 0.0001 (h), ***P = 0.0004 (i), *P = 0.0407 (j)). k Hepatic triglyceride (TG) content in Pten-/- mice treated with vehicle or C1632, as described in (a) (n = 4 mice/group, *P = 0.0412). l-o Serum TG (n = 4 mice/group), free fatty acids (FFA) (n = 3-4 mice/group,), insulin (n = 4 mice/group), and ALT levels (n = 4 mice/group, **P = 0.0077) in Pten-/- mice treated with vehicle or C1632, as described in (a). Numbers to the left of the blots indicate molecular weight markers. Values are mean ± SEM. *P < 0.05; **P < 0.01; ***P  <  0.001, ****P < 0.0001. Groups were compared using two-tailed unpaired Student’s t-test. Source data are provided as a Source Data file.

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