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Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
Published on: October 23, 2018
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STE20-type kinase TAOK3 regulates hepatic lipid partitioning
Ying Xia1, Mara Caputo1, Emmelie Cansby1
1Department of Chemistry and Molecular Biology, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
Molecular Metabolism
|October 11, 2021
Summary
The protein kinase TAOK3 promotes nonalcoholic fatty liver disease (NAFLD) by increasing liver fat accumulation. Inhibiting TAOK3 reduces NAFLD progression and liver lipotoxicity.
Area of Science:
- Hepatology
- Molecular Biology
- Biochemistry
Background:
- Nonalcoholic fatty liver disease (NAFLD) is a growing global health concern characterized by excessive fat in liver cells.
- The role of specific proteins, like STE20-type protein kinase TAOK3, in NAFLD pathogenesis is under investigation.
Purpose of the Study:
- To investigate the role of TAOK3 in the development and worsening of human NAFLD.
- To determine the correlation between TAOK3 expression and NAFLD severity.
Main Methods:
- Analysis of TAOK3 mRNA levels in liver biopsies from 62 individuals with varying NAFLD severity.
- In vitro studies using immortalized human hepatocytes to assess the impact of TAOK3 overexpression or knockdown on lipid metabolism, oxidative stress, and endoplasmic reticulum stress.
- Immunofluorescence microscopy to determine the subcellular localization of TAOK3.
Main Results:
- TAOK3 mRNA levels positively correlated with hepatic steatosis, inflammation, and ballooning in human NAFLD liver biopsies.
- TAOK3 overexpression in hepatocytes increased lipid storage by inhibiting fatty acid oxidation and triacylglycerol secretion, while enhancing lipid synthesis.
- TAOK3 knockdown reduced lipid deposition by promoting fatty acid oxidation and triacylglycerol efflux and suppressing lipogenesis.
- Altered TAOK3 levels modulated oxidative and endoplasmic reticulum stress.
- TAOK3 was localized to intracellular lipid droplets in human and mouse hepatocytes.
Conclusions:
- Hepatic TAOK3 is a key regulator of liver lipotoxicity and susceptibility to NAFLD.
- TAOK3 acts as a critical node in controlling lipid metabolism and stress responses within hepatocytes, influencing NAFLD progression.
Keywords:
Intrahepatocellular lipid dropletsLiver lipid metabolismNonalcoholic fatty liver diseaseNonalcoholic steatohepatitisTAOK3More Related Videos
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