Anti-adipogenic effects of <i>N</i> -acetyltyramine from termite-associated <i>Streptomyces</i> sp. M45

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 <i>Streptomyces</i> sp. M45. Chemical investigation of the extract from cultured <i>Streptomyces</i> sp. M45 led to the isolation of six metabolites (1-6). Structures were determined as 2-acetamido-3-hydroxybenzoic acid (1), <i>N</i>-acetyltyramine (2), deoxyuridine (3), cyclo(L-Pro-L-Leu) (4), cyclo(L-Pro-D-Leu) (5), and cyclo(L-Pro-L-Phe) (6) <i>via</i> 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/EBPα, C/EBPβ, and SREBP2). Among these, <i>N</i>-acetyltyramine (2) significantly inhibited adipocyte differentiation without impairing cell viability. Mechanistically, compound 2 downregulated the expression of key adipogenic genes including C/EBPα, SREBP2, FASN, UCP2, and leptin. These findings substantiate its potential as a modulator of obesity-related pathways in 3T3-L1 adipocytes.