Ablation of Iah1, a candidate gene for diet-induced fatty liver, does not affect liver lipid accumulation in mice

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a pathological condition caused by excess triglyceride deposition in the liver. The SMXA-5 severe fatty liver mouse model has been established from the SM/J and A/J strains. To explore the genetic factors involved in fatty liver development in SMXA-5 mice, we had previously performed quantitative trait locus (QTL) analysis, using (SM/J×SMXA-5)F2 intercross mice, and identified Fl1sa on chromosome 12 (centromere-53.06 Mb) as a significant QTL for fatty liver. Furthermore, isoamyl acetate-hydrolyzing esterase 1 homolog (Iah1) was selected as the most likely candidate gene for Fl1sa. Iah1 gene expression in fatty liver-resistant A/J-12 SM mice was significantly higher than in fatty liver-susceptible A/J mice. These data indicated that the Iah1 gene might be associated with fatty liver development. However, the function of murine Iah1 remains unknown. Therefore, in this study, we created Iah1 knockout (KO) mice with two different backgrounds [C57BL/6N (B6) and A/J-12 SM (A12)] to investigate the relationship between Iah1 and liver lipid accumulation. Liver triglyceride accumulation in Iah1-KO mice of B6 or A12 background did not differ from their respective Iah1-wild type mice under a high-fat diet. These results indicated that loss of Iah1 did not contribute to fatty liver. On the other hands, adipose tissue dysfunction causes lipid accumulation in ectopic tissues (liver, skeletal muscle, and pancreas). To investigate the effect of Iah1 deficiency on white adipose tissue, we performed DNA microarray analysis of epididymal fat in Iah1-KO mice of A12 background. This result showed that Iah1 deficiency might decrease adipokines Sfrp4 and Metrnl gene expression in epididymal fat. This study demonstrated that Iah1 deficiency did not cause liver lipid accumulation and that Iah1 was not a suitable candidate gene for Fl1sa.

Meteorin-like/Metrnl, a novel secreted protein implicated in inflammation, immunology, and metabolism: A comprehensive review of preclinical and clinical studies

“…A similar clinical context study was also reported by Grander et al (30), which found Metrnl expression was decreased in hepatic-and adipose tissues after BS in non-alcoholic fatty liver disease (NAFLD). Interestingly, Metrnl has been identified as a target protein with Iah1, a candidate gene for diet-induced NAFLD (133). Maybe Metrnl as one of the hepatokines play role in NAFLD progress but further investigations are needed to clarify the mechanism.…”

Data-independent acquisition mass spectrometry quantitative proteomic analysis reveals that skin aging-related proteins differ between men and women

“…The increase of Cd36 mRNA level in the liver is related to the increase of hepatocellular carcinoma and the accumulation of hepatic triglycerides. Therefore, the expression of Iah1 can avoid the formation of fatty liver (Masuya et al, 2020;Kobayashi et al, 2016). Aging is related to the imbalance of glucose and lipid metabolism.…”