Panx1 deficiency exacerbates GAN diet-induced obesity by destabilizing β-catenin via GSK3β

Obesity is a global health challenge and a major risk factor for metabolic diseases. Here, we show that Panx1-deficient mice develop severe obesity when fed a Gubra-Amylin (GAN) diet, characterized by adipocyte hypertrophy and disrupted lipid metabolism, while no such phenotype is observed on a conventional high-fat diet. Mechanistically, Panx1 deficiency leads to reduced non-phosphorylated β-catenin levels and its downstream targets, indicating impaired Wnt/β-catenin signaling. We further demonstrate that Panx1 interacts with β-catenin and GSK-3β, stabilizing β-catenin and preventing its degradation. Loss of Panx1 reduces β-catenin activity, impairs adipocyte hyperplasia, and promotes hypertrophic adipose expansion, thereby exacerbating obesity. These findings establish Panx1 as a key regulator of adipose tissue remodeling and suggest its potential as a tissue-specific target for obesity and related metabolic disorders.