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

IF 3.9 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular and cell biology of lipids Pub Date : 2025-04-21 DOI:10.1016/j.bbalip.2025.159616

MOHAMED ALI AWAD , Wenjiao Gu , Shuangyi Li , Yujie Wei , Yu Tang , Youming Shi , HAVYARIMANA JUVENAL , Ying Jiang , Ting Liu , Limei Shuai , Zhiming Wang , Bofan Wu , Xiaochun Zhou , Futian Tang

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引用次数: 0

Abstract

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.

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Calpain-1是载脂蛋白E敲除小鼠肝功能和代谢异常所必需的，通过小动物MRI和PET-CT无创评估

我们之前报道过calpain-1敲除（KO）可改善高脂饮食（HFD） C57小鼠的肝功能障碍。本研究将载脂蛋白E KO （ApoE KO）小鼠与calpain-1 KO小鼠杂交，获得ApoE/calpain-1双KO （A × C DKO）小鼠，研究calpain-1在肝功能和代谢异常中的作用，采用MRI和PETCT无创评价。将小鼠分为C57小鼠饲喂标准饲料（C57 + SD组）和C57 + HFD、calpain-1 KO + HFD、ApoE KO + HFD和A × C DKO + HFD组。测定血清白蛋白（ALB）含量、天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）活性以及血清和（或）肝脏肿瘤坏死因子（TNF-α）和白细胞介素-6 （IL-6）含量。采用MRI评估肝脏脂肪分数（FF）。注射18f -氟脱氧葡萄糖（FDG）后，用PETCT检测肝脏代谢。结果显示，与C57 + HFD和ApoE KO + HFD小鼠相比，calpain-1 KO + HFD和A × C DKO + HFD小鼠的ALB、AST、ALT、TNF-α和IL-6水平分别降低。此外，calpain-1 KO可改善肝脏FDG代谢。然而，calpain-1 KO不影响血清和肝脏的脂质谱和肝脏的FF。结果表明，缺乏calpain-1可通过抑制炎症改善血脂异常引起的肝功能和代谢异常。此外，小动物MRI和PETCT是无创评估小鼠肝脏脂质沉积和物质代谢的理想方法。

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来源期刊

Biochimica et biophysica acta. Molecular and cell biology of lipids 生物-生化与分子生物学

CiteScore

11.00

自引率

2.10%

发文量

109

审稿时长

53 days

期刊介绍： BBA Molecular and Cell Biology of Lipids publishes papers on original research dealing with novel aspects of molecular genetics related to the lipidome, the biosynthesis of lipids, the role of lipids in cells and whole organisms, the regulation of lipid metabolism and function, and lipidomics in all organisms. Manuscripts should significantly advance the understanding of the molecular mechanisms underlying biological processes in which lipids are involved. Papers detailing novel methodology must report significant biochemical, molecular, or functional insight in the area of lipids.