Abstract | PURPOSE: METHODS: PNPLA3 148I knockin HepG2 cells were constructed using the Cas9/sgRNA system. Oil Red O staining combined with TG quantification was used to evaluate lipid accumulation. Western blotting and qRT-qPCR were conducted, respectively, to measure the protein and mRNA expression of lipid metabolic and endoplasmic reticulum (ER) stress-related inflammatory markers. PNPLA3 I148M was genotyped in type 2 diabetics using Sanger sequencing. The exenatide-induced changes in liver fat content and other clinical parameters were compared between PNPLA3 I148M genotypes. RESULTS:
Lipid deposition increased in both PNPLA3 148I/I and 148M/M HepG2 cells treated with palmitoleic acid, while cells with 148M/M had a higher TG content than those with 148I/I. Exendin-4 treatment was showed to be more significant in 148I/I cells than in 148M/M cells in terms of reducing the intrahepatic fat content, inhibiting SREBP-1c and ER stress-related inflammation, and activating AMPK-ACC lipid oxidation pathway. In patients with type 2 diabetes, 24-week treatment with exenatide improved liver fat content in patients carrying PNPLA3 148I/I better than in patients with 148M/M. CONCLUSIONS:
|
Authors | Yunzhi Chen, Xuemei Yan, Xiao Xu, Shuhua Yuan, Fen Xu, Hua Liang |
Journal | Endocrine
(Endocrine)
Vol. 70
Issue 3
Pg. 517-525
(12 2020)
ISSN: 1559-0100 [Electronic] United States |
PMID | 32862405
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Membrane Proteins
- Exenatide
- Lipase
- adiponutrin, human
|
Topics |
- Diabetes Mellitus, Type 2
(drug therapy, genetics)
- Exenatide
(pharmacology)
- Genetic Predisposition to Disease
- Genotype
- Hep G2 Cells
- Humans
- Lipase
(genetics)
- Liver
- Membrane Proteins
(genetics)
- Non-alcoholic Fatty Liver Disease
(drug therapy, genetics)
|