High fat diet could cause kidney injury, and the underlying mechanism remains incompletely understood. In this study, we investigated the role of Wnt signaling in this process. Mice were fed with high-fat diet in vivo, and podocytes were stimulated with
palmitate in vitro. In mice fed with high-fat diet, renal function was impaired, accompanied by induction of various proinflammatory
cytokines and
proteinuria. Renal expression of Wnt
ligands was also significantly induced, with Wnt1 and Wnt3a being the most pronounced, in high-fat diet mice, compared with normal diet controls. Intervention with
ICG-001, a small molecule Wnt/β-
catenin inhibitor, improved renal function, inhibited proinflammatory
cytokines expression, reduced
proteinuria and alleviated podocyte injury. In
palmitate-treated podocytes, intracellular
lipid deposition was increased, Wnt1 and Wnt3a expression was up-regulated, which was accompanied by an increased proinflammatory
cytokines expression and podocyte injury. These lesions caused by
palmitate were largely alleviated by
ICG-001. Furthermore,
ICG-001 also restored the expression of phosphorylated AMPK repressed by
palmitate in podocytes or a high-fat diet in mice. These studies suggest that Wnt/β-
catenin signaling is involved in the pathogenesis of high-fat diet-induced kidney injury. Targeting this signaling may be a potential therapeutic strategy for alleviating
obesity-related nephropathy.