Protein kinase MST3 modulates lipid homeostasis in hepatocytes and correlates with nonalcoholic steatohepatitis in humans.
Animals
Cell Compartmentation
Cells, Cultured
Diet, High-Fat
/ adverse effects
Dietary Fats
/ pharmacokinetics
Female
Gene Knockdown Techniques
Hepatocytes
/ metabolism
Homeostasis
Humans
Lipid Droplet Associated Proteins
/ physiology
Lipid Droplets
/ metabolism
Lipid Metabolism
Liver
/ metabolism
Male
Mice
Mice, Inbred C57BL
Mitochondria, Liver
/ metabolism
Non-alcoholic Fatty Liver Disease
/ metabolism
Organ Specificity
Oxidation-Reduction
Oxidative Stress
Protein Serine-Threonine Kinases
/ analysis
RNA Interference
RNA, Small Interfering
/ genetics
Rats
Triglycerides
/ metabolism
ectopic lipid storage
intrahepatocellular lipid droplets
liver lipid metabolism
nonalcoholic fatty liver disease
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
pubmed:
8
6
2019
medline:
2
6
2020
entrez:
8
6
2019
Statut:
ppublish
Résumé
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,
Identifiants
pubmed: 31173506
doi: 10.1096/fj.201900356RR
doi:
Substances chimiques
Dietary Fats
0
Lipid Droplet Associated Proteins
0
RNA, Small Interfering
0
Triglycerides
0
STK24 protein, human
EC 2.7.1.-
Stk24 protein, mouse
EC 2.7.1.-
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM