Secreted Frizzled-Related Protein 5 Mediates Wnt5a Expression in Microcystin-Leucine-Arginine-Induced Liver Lipid
Mei Yan Yang1, Fu Rong Yu2, Qian Qian Ji1
1Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei 230032, Anhui, China.
Objective:
Microcystin-leucine-arginine (MC-LR) exposure induces lipid metabolism disorders in the liver. Secreted frizzled-related protein 5 (SFRP5) is a natural antagonist of winglesstype MMTV integration site family, member 5A (Wnt5a) and an anti-inflammatory adipocytokine. In this study, we aimed to investigate whether MC-LR can induce lipid metabolism disorders in hepatocytes and whether SFRP5, which has anti-inflammatory effects, can alleviate the effects of hepatic lipid metabolism by inhibiting the Wnt5a/Jun N-terminal kinase (JNK) pathway.
Methods:
We exposed mice to MC-LR in vivo to induce liver lipid metabolism disorders. Subsequently, mouse hepatocytes that overexpressed SFRP5 or did not express SFRP5 were exposed to MC-LR, and the effects of SFRP5 overexpression on inflammation and Wnt5a/JNK activation by MC-LR were observed.
Results:
MC-LR exposure induced liver lipid metabolism disorders in mice and significantly decreased SFRP5 mRNA and protein levels in a concentration-dependent manner. SFRP5 overexpression in AML12 cells suppressed MC-LR-induced inflammation. Overexpression of SFRP5 also inhibited Wnt5a and phosphorylation of JNK.
Conclusion:
MC-LR can induce lipid metabolism disorders in mice, and SFRP5 can attenuate lipid metabolism disorders in the mouse liver by inhibiting Wnt5a/JNK signaling.
Insights
Microcystin-leucine-arginine (MC-LR) causes liver lipid disorders. Secreted frizzled-related protein 5 (SFRP5) alleviates these disorders by inhibiting the Wnt5a/JNK pathway, offering a potential therapeutic target.
Area of Science:
- Hepatology
- Toxicology
- Molecular Biology
Background:
- Microcystin-leucine-arginine (MC-LR) is a potent hepatotoxin known to disrupt lipid metabolism.
- Secreted frizzled-related protein 5 (SFRP5) is an adipocytokine with anti-inflammatory properties and an antagonist of the Wnt5a signaling pathway.
Purpose of the Study:
- To investigate the impact of MC-LR on lipid metabolism in hepatocytes.
- To determine if SFRP5 can mitigate MC-LR-induced hepatic lipid disorders.
- To elucidate the role of the Wnt5a/Jun N-terminal kinase (JNK) pathway in MC-LR's effects and SFRP5's protective mechanism.
Main Methods:
- MC-LR was administered to mice to induce liver lipid metabolism disorders.
- Mouse hepatocytes with and without SFRP5 overexpression were exposed to MC-LR.
- Inflammation, Wnt5a, and JNK pathway activation were assessed in response to MC-LR and SFRP5 manipulation.
Main Results:
- MC-LR exposure led to significant liver lipid metabolism disorders in mice.
- MC-LR significantly reduced SFRP5 mRNA and protein levels in a dose-dependent manner.
- SFRP5 overexpression in hepatocytes suppressed MC-LR-induced inflammation and inhibited Wnt5a signaling and JNK phosphorylation.
Conclusions:
- MC-LR induces hepatic lipid metabolism disorders through mechanisms involving the Wnt5a/JNK pathway.
- SFRP5 attenuates MC-LR-induced lipid metabolism disorders in the liver by inhibiting the Wnt5a/JNK signaling pathway.
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