STE20-type kinase TAOK3 regulates hepatic lipid partitioning

• DOI: 10.1016/j.molmet.2021.101353
• Publication Date: 2021-10-09T14:18:51Z
• Authors: Ying Xia; Mara Caputo; Emmelie Cansby; Sumit Kumar Anand; Silva Sütt; Marcus Henricsson; Rando Porosk; Hanns-Ulrich Mars...; Matthias Blüher; Margit Mahlapuu
• Keywords: Lipid droplet; Steatosis; Lipotoxicity; Lipogenesis; Hepatic stellate cell

Nonalcoholic fatty liver disease (NAFLD), defined by excessive lipid storage in hepatocytes, has recently emerged as a leading global cause of chronic disease. The aim this study was to examine the role STE20-type protein kinase TAOK3, which previously been shown associate with hepatic droplets, initiation and aggravation human NAFLD.The correlation between TAOK3 mRNA expression severity NAFLD investigated biopsies from 62 individuals. In immortalized intracellular fat deposition, metabolism, oxidative endoplasmic reticulum stress were analyzed when overexpressed or knocked down small interfering RNA. Subcellular localization characterized mouse hepatocytes immunofluorescence microscopy.We found that transcript levels positively correlated key lesions (i.e., steatosis, inflammation, ballooning). Overexpression cultured exacerbated inhibiting β-oxidation triacylglycerol secretion while enhancing synthesis. Conversely, silencing attenuated deposition stimulating mitochondrial acid oxidation efflux suppressing lipogenesis. We also aggravated decreased oxidative/endoplasmic increased reduced levels, respectively. subcellular confined droplets.This provides first evidence droplet-coating is critical regulatory node controlling lipotoxicity susceptibility NAFLD.