High Fat Diet Induces Kidney Injury via Stimulating Wnt/β-Catenin Signaling

Area of Science:

• Nephrology
• Molecular Biology
• Metabolic Diseases

Background:

• High-fat diets are linked to kidney injury, but mechanisms are unclear.
• Wnt signaling is implicated in various cellular processes, including kidney development and disease.

Purpose of the Study:

• To investigate the role of Wnt/β-catenin signaling in high-fat diet-induced kidney injury.
• To evaluate the therapeutic potential of Wnt/β-catenin inhibition.

Main Methods:

• Mice were fed high-fat diets (in vivo); podocytes were treated with palmitate (in vitro).
• Wnt ligand expression, kidney function, proteinuria, and podocyte injury were assessed.
• Wnt/β-catenin signaling was inhibited using ICG-001.

Main Results:

• High-fat diet induced kidney dysfunction, inflammation, and proteinuria in mice.
• Wnt1 and Wnt3a expression increased in high-fat diet mice and palmitate-treated podocytes.
• ICG-001 treatment improved renal function, reduced inflammation and proteinuria, and protected podocytes.
• ICG-001 also restored phosphorylated AMPK levels suppressed by palmitate or high-fat diet.

Conclusions:

• Wnt/β-catenin signaling plays a significant role in high-fat diet-induced kidney injury.
• Targeting Wnt/β-catenin signaling may be a viable therapeutic strategy for obesity-related nephropathy.