Hepatic-specific vitamin D receptor downregulation alleviates aging-related metabolic dysfunction-associated steatotic liver disease

Figure 2 Establishment of a mouse aging model and aggravation of hepatic steatosis after senescence. A: Β-Galactosidase staining (× 200) of liver sections from 3-month-old telomerase RNA component knockout mice (Terc^-/-) or wild-type (WT) mice; B: Protein expression levels of P16, P21, and P53 and corresponding quantitative results, and mRNA levels of P16, P21, and P53 in 3-month-old Terc^-/- or WT mice; C: Weights, liver weights, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TGs), and total cholesterol (TC) and hepatic levels of TGs and TC in 3-month-old Terc^-/- or WT mice; D: Hematoxylin-eosin (HE) and Oil Red O staining (× 200) of the liver sections; E-H: The 3-month-old Terc^-/- or WT mice were fed a high-fat diet or standard chow diet (SCD) for 8 weeks to establish a model of metabolic dysfunction-associated steatotic liver disease; Weights and changes in weight (E); Glucose tolerance test and associated area under the curve. Insulin tolerance test and associated area under the curve (F); Liver weights, liver-to-body weight ratios, serum levels of ALT, AST, TGs, and TC, and hepatic levels of TGs and TC (G); HE and Oil Red O staining (× 200) of the liver sections (H); I-K: Three-month-old Terc^-/- or WT mice were fed a methionine/choline-deficient diet or SCD for 6 weeks to establish a model of metabolic dysfunction-associated steatohepatitis; Weights and changes in weight (I); Liver weights, liver-to-body weight ratio, serum levels of ALT, AST, TGs, and TC, and hepatic levels of TGs (J); HE and Oil Red O staining (× 200) of the liver sections. Protein levels and mRNA levels were normalized to those of glyceraldehyde-3-phosphate dehydrogenase (K). The data are presented as the means ± SDs. ^aP < 0.05. ^bP < 0.01. ^cP < 0.001. P as determined via student’s t tests and one-way analysis of variance with Tukey’s correction. WT: Wild-type; HE: Hematoxylin-eosin; MCD: Methionine-choline-deficient diet; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TG: Triglycerides; TC: Total cholesterol; SCD: Standard chow diet; HFD: High-fat diet; GTT: Glucose tolerance test; ITT: Insulin tolerance test; AUC: Area under the curve; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase.