A mouse model of short-term, diet-induced fatty liver with abnormal cardiolipin remodeling via downregulated Tafazzin gene expression.

BACKGROUND Cardiolipin (CL) helps maintain mitochondrial structure and function. Here we investigated whether a high carbohydrate diet (HCD) fed to mice for a short term (5 days) can modulate the CL level including that of monolysoCL (MLCL) in the liver. RESULTS Total CL in the HCD group was 22% lower than that in the normal chow diet (NCD) group (P <0.05). CL72:8 level strikingly decreased by 93% (P <0.0001), whereas total nascent CL (CLs other than CL72:8) increased (P <0.01) in the HCD group. Moreover, total MLCL in the HCD group increased by 2.4-fold compared with that in the NCD group (P <0.05). Tafazzin expression in the HCD group was significantly downregulated compared with that in the NCD group (P <0.05). A strong positive correlation between nascent CL and total MLCL (r = 0.955, P <0.0001), and a negative correlation between MLCL and Tafazzin expression (r = -0.593, P = 0.0883) were observed. CONCLUSION HCD modulated fatty acid compositions of CL and MLCL via Tafazzin in the liver, which could lead to mitochondrial dysfunction. This model may be useful for elucidating the relationship between fatty liver and mitochondrial dysfunction. This article is protected by copyright. All rights reserved.