Bcat2-Mediated Branched-Chain Amino Acid Catabolism Is Linked to the Aggravated Inflammation in Obese with Psoriasis Mice
MOLECULAR NUTRITION & FOOD RESEARCH(2024)
摘要
Scope: 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 gamma) 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 gamma-STAT3 exacerbate inflammation in psoriasis with obesity. Obesity significantly amplifies IL-7 signaling and exacerbates psoriasis. Bcat2-mediated BCAAs metabolism is inhibited in obesity with psoriasis. The amplified IL-17 signaling pathway is mediated by PPAR gamma-STAT3 axis. Bcat2 may possess a potentially advantageous function in the mitigation or management of obesity linked to psoriasis and immune system disorders. image
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关键词
Bcat2, branched-chain amino acid, healthy, obesity,psoriasis
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