Modulation of Obesity-Related Lipid Metabolism by Sulforaphane Through AMPK-Centered Molecular Networks.

Sulforaphane (SFN), an isothiocyanate produced from glucoraphanin in cruciferous vegetables, has been associated with the regulation of lipid storage, fatty acid oxidation, and autophagic lipid turnover. Therefore, in the current narrative review, AMPK-centered mechanisms were critically evaluated by distinguishing pathway association from experimentally demonstrated AMPK dependence. In cell and animal models, SFN treatment was associated with ACC phosphorylation, inhibition of mTORC1-SREBP signaling, CPT-1-related fatty acid oxidation, PGC-1α/PPAR-α transcriptional regulation, and ULK1-mediated lipophagy. However, most studies measured AMPK phosphorylation without pharmacological or genetic suppression, and one adipocyte study showed decreased AMPK phosphorylation during SFN-induced lipolysis. These findings indicate that SFN signaling can vary depending on the model, dose, and measured endpoint. Human studies have also shown highly variable SFN exposure and limited or inconsistent effects on lipid and glycemic outcomes, but AMPK-mediated lipid remodeling has not been directly demonstrated in target tissues. In addition, food matrix, myrosinase activity, dose, gut microbiota, and SFN-NIT formation can influence systemic exposure. Therefore, AMPK may be considered an important component of a broader SFN-responsive network rather than an exclusive mechanism. Further standardized human studies are required to evaluate quantified SFN exposure, lipid-related outcomes, tissue-relevant pathway biomarkers, and long-term safety.