Involvement of SIK3 in Glucose and Lipid Homeostasis in Mice
Open Access
- 25 May 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (5), e37803
- https://doi.org/10.1371/journal.pone.0037803
Abstract
Salt-inducible kinase 3 (SIK3), an AMP-activated protein kinase-related kinase, is induced in the murine liver after the consumption of a diet rich in fat, sucrose, and cholesterol. To examine whether SIK3 can modulate glucose and lipid metabolism in the liver, we analyzed phenotypes of SIK3-deficent mice. Sik3−/− mice have a malnourished the phenotype (i.e., lipodystrophy, hypolipidemia, hypoglycemia, and hyper-insulin sensitivity) accompanied by cholestasis and cholelithiasis. The hypoglycemic and hyper-insulin-sensitive phenotypes may be due to reduced energy storage, which is represented by the low expression levels of mRNA for components of the fatty acid synthesis pathways in the liver. The biliary disorders in Sik3−/− mice are associated with the dysregulation of gene expression programs that respond to nutritional stresses and are probably regulated by nuclear receptors. Retinoic acid plays a role in cholesterol and bile acid homeostasis, wheras ALDH1a which produces retinoic acid, is expressed at low levels in Sik3−/− mice. Lipid metabolism disorders in Sik3−/− mice are ameliorated by the treatment with 9-cis-retinoic acid. In conclusion, SIK3 is a novel energy regulator that modulates cholesterol and bile acid metabolism by coupling with retinoid metabolism, and may alter the size of energy storage in mice.Keywords
This publication has 61 references indexed in Scilit:
- Vitamin A Deficiency Associated with Enhanced Proliferation of Bile Duct Epithelial Cells in the Rat2010
- LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1The EMBO Journal, 2004
- Identification of a family of cAMP response element-binding protein coactivators by genome-scale functional analysis in mammalian cellsProceedings of the National Academy of Sciences, 2003
- TORCsMolecular Cell, 2003
- Peroxisome proliferator-activated receptor alpha (PPARalpha)-mediated regulation of multidrug resistance 2 (Mdr2) expression and function in miceBiochemical Journal, 2003
- ACTH-induced Nucleocytoplasmic Translocation of Salt-inducible KinasePublished by Elsevier BV ,2002
- Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinaseNature Medicine, 2002
- Salt-inducible Kinase Represses cAMP-dependent Protein Kinase-mediated Activation of Human Cholesterol Side Chain Cleavage Cytochrome P450 Promoter through the CREB Basic Leucine Zipper DomainPublished by Elsevier BV ,2002
- Regulation of Chemosensory Receptor Expression and Sensory Signaling by the KIN-29 Ser/Thr KinaseNeuron, 2002
- Hydrophilic bile salts enhance differential distribution of sphingomyelin and phosphatidylcholine between micellar and vesicular phases: potential implications for their effects in vivoJournal of Hepatology, 2001