Hepatic loss of Lissencephaly 1 (Lis1 ) induces fatty liver and accelerates liver tumorigenesis in mice

The Journal of Biological Chemistry
Xiaoling LiHai Song

Abstract

The liver is a major organ in lipid metabolism, and its malfunction leads to various diseases. Nonalcoholic fatty liver disease, the most common chronic liver disorder in developed countries, is characterized by the abnormal retention of excess lipid within hepatocytes and predisposes individuals to liver cancer. We previously reported that the levels of Lissencephaly 1 (LIS1, also known as PAFAH1B1) are down-regulated in human hepatocellular carcinoma. Following up on this observation, we found that genetic deletion of Lis1 in the mouse liver increases lipid accumulation and inflammation in this organ. Further analysis revealed that loss of Lis1 triggers endoplasmic reticulum (ER) stress and reduces triglyceride secretion. Attenuation of ER stress by addition of tauroursodeoxycholic acid (TUDCA) diminished lipid accumulation in the Lis1-deficient hepatocytes. Moreover, the Golgi stacks were disorganized in Lis1-deficient liver cells. Of note, the Lis1 liver-knockout mice exhibited increased hepatocyte ploidy and accelerated development of liver cancer after exposure to the liver carcinogen diethylnitrosamine (DEN). Taken together, these findings suggest that reduced Lis1 levels can spur the development of liver diseases from s...Continue Reading

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Citations

Nov 22, 2019·Frontiers in Oncology·Felix M BreharRadu M Gorgan
Jun 26, 2020·Molecular Biology of the Cell·Genki AmanoTaiichi Katayama
Aug 6, 2021·BMC Genomics·Christos DimitrakopoulosNiko Beerenwinkel
Aug 25, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jiacheng WuXuewen Zhang

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Datasets Mentioned

BETA
GSE48452
GM130

Methods Mentioned

BETA
GTPase
PCR
RNA-Seq
flow cytometry
glycosylation
light microscopy
FACS

Software Mentioned

Maverix Analytic Platform
Maverix

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