Lambda-cyhalothrin induces lipid accumulation in mouse liver is associated with AMPK inactivation

Area of Science:

• Toxicology
• Metabolic Disease
• Molecular Biology

Background:

• Synthetic pyrethroid insecticides like Lambda-cyhalothrin (LCT) are widely used.
• Previous research suggests pyrethroids may promote fat accumulation and impair liver function.
• The specific effects of LCT on hepatic lipid metabolism and its underlying cellular mechanisms remain unclear.

Purpose of the Study:

• To investigate the impact of LCT exposure on hepatic lipid metabolism and liver function in mice.
• To elucidate the cellular mechanisms involved in LCT-induced liver injury.
• To explore the potential role of AMPK (AMP-activated protein kinase) in mitigating LCT's effects.

Main Methods:

• ICR mice were orally administered LCT at doses of 0.4 mg/kg and 2 mg/kg.
• Hepatic lipid metabolism, oxidative stress markers, liver function, and gene expression (PPARγ, FASN, SREBP1c, PPARα, FGF21) were analyzed.
• Changes in the phosphorylation status of AMPK and ACC (acetyl-CoA carboxylase) were assessed.

Main Results:

• LCT exposure led to obesity, dyslipidemia, and hepatic steatosis (fatty liver) in mice.
• LCT induced oxidative stress, liver function impairment, and disorganized liver structure.
• Upregulation of PPARγ, FASN, and SREBP1c, alongside downregulation of PPARα and FGF21, and reduced AMPK/ACC phosphorylation were observed.

Conclusions:

• LCT at 0.4 mg/kg induces dyslipidemia and hepatic steatosis in mice.
• LCT-induced hepatic steatosis is linked to the AMPK signaling pathway and its downstream targets.
• Activation of AMPK presents a potential protective strategy against LCT-induced fatty liver disease.