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Protein kinase MST3 modulates lipid homeostasis in hepatocytes and correlates with nonalcoholic steatohepatitis in humans

Published on Jun 7, 2019in The FASEB Journal5.39
· DOI :10.1096/fj.201900356RR
Emmelie Cansby8
Estimated H-index: 8
,
Nagaraj M. Kulkarni1
Estimated H-index: 1
+ 9 AuthorsMargit Mahlapuu20
Estimated H-index: 20
Abstract
Ectopic lipid storage in the liver is considered the main risk factor for nonalcoholic steatohepatitis (NASH). Understanding the molecular networks controlling hepatocellular lipid deposition is therefore essential for developing new strategies to effectively prevent and treat this complex disease. Here, we describe a new regulator of lipid partitioning in human hepatocytes: mammalian sterile 20–like (MST) 3. We found that MST3 protein coats lipid droplets in mouse and human liver cells. Knockdown of MST3 attenuated lipid accumulation in human hepatocytes by stimulating β-oxidation and triacylglycerol secretion while inhibiting fatty acid influx and lipid synthesis. We also observed that lipogenic gene expression and acetyl-coenzyme A carboxylase protein abundance were reduced in MST3-deficient hepatocytes, providing insight into the molecular mechanisms underlying the decreased lipid storage. Furthermore, MST3 expression was positively correlated with key features of NASH (i.e., hepatic lipid content, lo...
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#1Emmelie Cansby (Sahlgrenska University Hospital)H-Index: 1
#2Esther Nuñez-Durán (Sahlgrenska University Hospital)H-Index: 6
Last.Margit Mahlapuu (Sahlgrenska University Hospital)H-Index: 20
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#1Scott L. Friedman (ISMMS: Icahn School of Medicine at Mount Sinai)H-Index: 106
#2Brent A. Neuschwander-Tetri (SLU: Saint Louis University)H-Index: 40
Last.Arun J. Sanyal (VCU: Virginia Commonwealth University)H-Index: 97
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#1Susanne Schuster (UCSD: University of California, San Diego)H-Index: 12
#2Daniel Cabrera (UC: Pontifical Catholic University of Chile)H-Index: 15
Last.Ariel E. Feldstein (UCSD: University of California, San Diego)H-Index: 55
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