Bcat2‐Mediated Branched‐Chain Amino Acid Catabolism Is Linked to the Aggravated Inflammation in Obese with Psoriasis Mice

Abstract

AbstractScope: The global prevalence of obesity has significantly increased, presenting a major health challenge. High‐fat diet (HFD)‐induced obesity is closely related to the disease severity of psoriasis, but the mechanism is not fully understood.Methods and results: The study utilizes the HFD‐induced obesity model along with an imiquimod (IMQ)‐induced psoriasis‐like mouse model (HFD‐IMQ) to conduct transcriptomics and metabolomic analyses. HFD‐induced obese mice exhibits more severe psoriasis‐like lesions compared to normal diet (ND)‐IMQ mice. The expression of genes of the IL‐17 signaling pathway (IL‐17A, IL‐17F, S100A9, CCL20, CXCL1) is significantly upregulated, leading to an accumulation of T cells and neutrophils in the skin. Moreover, the study finds that there is an inhibition of the branched‐chain amino acids (BCAAs) catabolism pathway, and the key gene branched‐chain amino transferase 2 (Bcat2) is significantly downregulated, and the levels of leucine, isoleucine, and valine are elevated in the HFD‐IMQ mice. Furthermore, the study finds that the peroxisome proliferator‐activated receptor gamma (PPAR γ) is inhibited, while STAT3 activity is promoted in HFD‐IMQ mice.Conclusion: HFD‐induced obesity significantly amplifies IL‐17 signaling and exacerbates psoriasis, with a potential role played by Bcat2‐mediated BCAAs metabolism. The study suggests that BCAA catabolism and PPAR γ‐STAT3 exacerbate inflammation in psoriasis with obesity.