Role of glucose metabolism reprogramming in keratinocytes in the link between psoriasis and metabolic syndrome

The mechanism linking psoriasis to metabolic syndrome (MetS) remains poorly understood. Recent reports indicate upregulation of glycolysis-related proteins in psoriatic keratinocytes (KCs). However, the role of glucose metabolism reprogramming in psoriatic KCs, psoriasis, and psoriasis with MetS remains unclear. In this study, we confirmed glucose metabolism reprogramming in psoriatic KCs by examining glycolysis-related genes, proteins, and metabolites. We found that inhibiting glucose metabolism reprogramming in psoriasiform KCs led to improvements in psoriasiform features. Notably, we observed enhanced glucose metabolism reprogramming in KCs within psoriatic skin lesions of patients with MetS. In vitro, high-glucose and high-fat culture intensified glucose metabolism reprogramming in psoriasiform KCs partially via the AKT/mTOR pathway. These findings highlight a strong link between the glycolytic switch and KC function and suggest that glucose metabolism reprogramming in KCs contributes to heightened psoriatic inflammation in MetS.