Adenoviral vectors encoding G5G8 (AdG5G8) disrupts hepatic cholesterol homeostasis. Obese db/db male mice and their lean littermates were administered control or AdG5G8 virus. A, Total hepatic lipids were extracted and cholesterol was measured by enzymatic colorimetric assay and expressed as mg/g wet tissue weight. B, Immunoblot and densitometric analysis of hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HM GCR) and low-density lipoprotein receptor (LDLR). C, Total RNA was extracted from liver 72 hours after viral administration and analyzed by reverse-transcriptase polymerase chain reaction for expression of genes involved in cholesterol synthesis and uptake. Data are mean±SEM (n=3–4). Horizontal lines terminating in vertical bars denote significant difference from control virus within genotype. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. CNX indicates calnexin; HM GCS, 3-hydroxy-3-methylglutaryl-coenzyme A synthase; SREBP, sterol regulatory element–binding protein; and VLDLR, very-LDLR.