Anti-adipogenic effects of N-acetyltyramine from termite-associated Streptomyces sp. M45

초록

Obesity remains a global health challenge, and novel small-molecule modulators of adipogenesis are urgently needed. Here, we investigated the anti-adipogenic potential of metabolites isolated from termite-associated Streptomyces sp. M45. Chemical investigation of the extract from cultured Streptomyces sp. M45 led to the isolation of six metabolites (1-6). Structures were determined as 2-acetamido-3-hydroxybenzoic acid (1), N-acetyltyramine (2), deoxyuridine (3), cyclo(l-Pro-l-Leu) (4), cyclo(l-Pro-d-Leu) (5), and cyclo(l-Pro-l-Phe) (6) via comprehensive analysis of nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS) data. Notably, the structure of the anthranilic acid derivative, 2-acetamido-3-hydroxybenzoic acid (1), was fully elucidated by 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry (HR-ESIMS), and DP4+ probability calculations, allowing us to correct previously reported 1H NMR resonances and to assign 13C NMR signals for the first time. Compounds 1-6 were evaluated for anti-adipogenic activity in differentiated 3T3-L1 cells by assessing lipid accumulation and the expression of adipogenic transcription factors (C/EBP alpha, C/EBP beta, and SREBP2). Among these, N-acetyltyramine (2) significantly inhibited adipocyte differentiation without impairing cell viability. Mechanistically, compound 2 downregulated the expression of key adipogenic genes including C/EBP alpha, SREBP2, FASN, UCP2, and leptin. These findings substantiate its potential as a modulator of obesity-related pathways in 3T3-L1 adipocytes.

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