Figure 3.
Fatty liver disease in postnatal Hmgcs2 knockout mice is rescued by early weaning. (A) Schematic representation of the early weaning protocol in postnatal WT and Hmgcs2-KO mice. Early-wean mice were separated from their mothers at p14 and transitioned from a high-fat breast milk to a standard laboratory chow diet. Suckling control mice remained on breast milk feeding until collection at postnatal day 21 (p21). (B) Hmgcs2 gene expression in the liver and (C) blood ketone levels of suckling and early-wean WT and Hmgcs2-KO mice at p21. (D) Liver weights (suckling WT/KO, n = 4; early-wean WT/KO, n = 5). (E) Representative liver image of Hmgcs2-KO suckling and early-wean mice at p21. (F) H&E and anti-Plin2 IHC staining of liver sections. Scale bar = 100 μm. Boxes indicate regions of higher magnification. (G) Histological liver fat quantification and (H) NAFLD activity score (NAS) (suckling WT, n = 5; suckling KO, n = 3; early-wean WT, n = 3; early-wean KO, n = 4; male and female mice combined). (I) Liver triglyceride concentrations of suckling and early-wean WT and Hmgcs2-KO mice at p21 (suckling WT/KO, n = 4; early-wean WT/KO, n = 5). (J) Hepatic gene expression analysis of lipid accumulation markers (Pparg, Fsp27, and Plin2). Data are represented as mean ± SEM. Statistical analysis was performed by two-way ANOVA. ∗P ≤ 0.05; ∗∗P ≤ 0.01; ∗∗∗P ≤ 0.001; ∗∗∗∗P ≤ 0.0001. (Created with BioRender.com).