Abstract
Chronic arsenic exposure is a risk factor for human fatty liver disease, and the ERK signaling pathway plays an important role in the regulation of liver lipid metabolism. However, whether ERK plays a role in the progression of arsenic-induced liver lipid metabolism disorder and the specific mechanism remain unclear. Here, by constructing a rat model of liver lipid metabolism disorder induced by chronic arsenic exposure, we demonstrated that ERK might regulate arsenic-induced liver lipid metabolism disorders through the PPAR signaling pathway. Arsenic could upregulate the expression of PPARγ and CD36 in the rat liver, decrease the expression of PPARα and CPT-1 in the rat liver, increase the organ coefficient of the rat liver, decrease the content of TG in rat serum, and promote fat deposition in the rat liver. In the arsenic-induced rat model of hepatic lipid metabolism disorder, we found that the expression of p-ERK was increased. In order to further explore whether the ERK signaling pathway was involved in arsenic-induced liver lipid metabolism disorder, we exposed L-02 cells to different arsenic concentrations, and the results showed that arsenic significantly increased the expression of P-ERK in L-02 cells in a dose-dependent manner. We further treated L-02 cells with ERK inhibitors and found that the expression of TG, PPARα, and CPT-1 in L-02 cells increased, while the expression of P-ERK, PPARγ, and CD36 decreased. In conclusion, ERK may be involved in arsenic-induced liver lipid metabolism disorder by regulating the PPAR signaling pathway. These findings are expected to provide a new targeting strategy for arsenic-induced liver lipid metabolism disorder.
Highlights
Arsenic is a common environmental poison, which is ubiquitous in water, coal, air, soil, and food
These results indicated that the model of liver lipid metabolism disorder induced by arsenic had been established successfully
The results showed that the expressions of PPARγ and CD36 mRNA and PPARγ protein were increased in L-02 cells in the NaAsO2 group and the expressions of PPARα, CPT-1, Sterol regulatory element-binding protein (SREBP)-1C, and fatty acid synthase (FASN) mRNA and PPARα and SREBP-1c proteins were decreased, compared with the control group
Summary
Arsenic is a common environmental poison, which is ubiquitous in water, coal, air, soil, and food. The incidence of arsenic exposure disease can be slightly reduced through health education, prohibition of the collection of high-arsenic coal, and renovation of stove facilities, the pathogenic mechanism of arsenic is unclear. It is very important to study the pathogenic mechanism of arsenic and identify possible regulatory targets. The liver is one of the main target organs of arsenic poisoning [6]. Previous studies have shown that chronic arsenic exposure can cause liver injury, hepatitis, liver fibrosis, cirrhosis, liver cancer, and other related malignant diseases [7, 8]. Population epidemiological investigations and experimental studies have confirmed that arsenic can cause liver damage. The liver damage caused by arsenic is mainly
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