Calpain-1 is required for abnormality of liver function and metabolism in apolipoprotein E knockout mouse evaluated noninvasively by small animal MRI and PET-CT.

We previously reported that calpain-1 knockout (KO) improved liver dysfunction in C57 mouse fed with high-fat diet (HFD). In the present study, Apolipoprotein E KO (ApoE KO) mouse was hybridized with calpain-1 KO mouse to obtain ApoE/calpain-1 double KO (A × C DKO) mouse to investigate role of calpain-1 in abnormality of liver function and metabolism evaluated noninvasively with MRI and PETCT. Mice were divided into C57 mice fed with standard diet (C57 + SD group) and C57 + HFD, calpain-1 KO + HFD, ApoE KO + HFD and A × C DKO + HFD groups fed with HFD. Contents of albumin (ALB), activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum and tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) in serum and/or liver were measured. Fat fraction (FF) in liver was evaluated using MRI. Liver metabolism was measured using PETCT after injection of 18F-Fluorodeoxyglucose (FDG). The results showed that levels of ALB, AST, ALT, TNF-α, and IL-6 in calpain-1 KO + HFD and A × C DKO + HFD mice were decreased compared with that of the matched C57 + HFD and ApoE KO + HFD mice, respectively. In addition, calpain-1 KO improved FDG metabolism in the liver. However, calpain-1 KO did not affect lipid profiles in serum and liver and FF in liver. The results suggested that calpain-1 deficiency improves dyslipidemia-induced abnormality of liver function and metabolism through inhibition of inflammation. In addition, small animal MRI and PETCT are ideal approaches for noninvasively evaluating lipid deposition and substance metabolism in liver of mice.