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The microbial metabolite desaminotyrosine is a potent antiobesity agent with potential effects on white adipose tissue remodeling in mice #MMPMID41340566
Huang H; Bu H; Liao L; Xiang Y; Chen Q; Fu G; Cheng W; Kou Y; Liu Z; Zheng K; Wang Y; Wei Y
Gut Microbes 2025[Dec]; 17 (1): 2587400 PMID41340566show ga
OBJECTIVES: White adipose tissue plays a critical role in obesity, as its dysfunction can impair lipid homeostasis. We previously demonstrated that desaminotyrosine (DAT), a microbial metabolite, prevents high-fat diet (HFD)-induced body weight gain in mice, but the role of DAT on white adipocyte is unknown. Here, we investigated the role of DAT in host metabolic health and its therapeutic potentials in treating obesity. METHODS: In this study, we employed a pharmacological approach by administering DAT to mice. These mice were subjected to HFD feeding to establish overweight model, followed by DAT treatment. The effect of DAT on white adipocytes were studied using both in vivo and in vitro models. RESULTS: Our data indicated that DAT is a potent weight loss chemical for obesity treatment. This is related to DAT's dual-function in regulating white adipose tissue remodeling. DAT enhances mature white adipocyte-autonomous fat disposal through sustained lipolysis and augmented expression of carnitine palmitoyltransferase I family protein CPT1A, a critical enzyme facilitating fatty acid oxidation (FAO), especially under lipolytic-inducing conditions. In the meantime, it blocks white adipogenesis via FAO-dependent pathway potentiation. CONCLUSIONS: Collectively, these data demonstrate that DAT is a potent antiobesity agent with potential effects on white adipose tissue remodeling. This study provides a novel pharmacological strategy targeting white adipocyte plasticity for treating metabolic disorders.