Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 24, Issue 5, Pages -Publisher
MDPI
DOI: 10.3390/ijms24054315
Keywords
glucokinase; GCK-MODY; hepatic lipid metabolism; inflammation; lipotoxicity
Ask authors/readers for more resources
This study investigates the effects of GCK inactivation on hepatic lipid metabolism and inflammation in GCK-MODY patients. The results show that GCK-MODY individuals have a cardioprotective lipid profile and GCK inactivation alleviates lipid accumulation and decreases inflammation-related gene expression. The study also reveals that GCK inactivation alters hepatic lipid metabolism and is regulated by enzymes involved in lipogenesis, lipolysis, fatty acid beta-oxidation, and the Kennedy pathway.
Glucokinase-maturity onset diabetes of the young (GCK-MODY) is a kind of rare diabetes with low incidence of vascular complications caused by GCK gene inactivation. This study aimed to investigate the effects of GCK inactivation on hepatic lipid metabolism and inflammation, providing evidence for the cardioprotective mechanism in GCK-MODY. We enrolled GCK-MODY, type 1 and 2 diabetes patients to analyze their lipid profiles, and found that GCK-MODY individuals exhibited cardioprotective lipid profile with lower triacylglycerol and elevated HDL-c. To further explore the effects of GCK inactivation on hepatic lipid metabolism, GCK knockdown HepG2 and AML-12 cell models were established, and in vitro studies showed that GCK knockdown alleviated lipid accumulation and decreased the expression of inflammation-related genes under fatty acid treatment. Lipidomic analysis indicated that the partial inhibition of GCK altered the levels of several lipid species with decreased saturated fatty acids and glycerolipids including triacylglycerol and diacylglycerol, and increased phosphatidylcholine in HepG2 cells. The hepatic lipid metabolism altered by GCK inactivation was regulated by the enzymes involved in de novo lipogenesis, lipolysis, fatty acid beta-oxidation and the Kennedy pathway. Finally, we concluded that partial inactivation of GCK exhibited beneficial effects in hepatic lipid metabolism and inflammation, which potentially underlies the protective lipid profile and low cardiovascular risks in GCK-MODY patients.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available