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Recently, the relationship between nutrients and health is becoming since natural dietary products as polyphenols are being considered by their potential for the management of several diseases. We aimed to investigate the capacity of Lippia citriodora compounds to modulate AMP-activated protein kinase activity (AMPK) on a hypertrophic adipocyte model. HPLC semi-preparative purification method and reverse phase high performance liquid chromatography coupled to time-of-flight mass detection with electrospray ionization (RP-HPLC-ESI-TOF/MS) were used to obtain de compounds from L. citriodora extract. AMPK activity was measured on the hypertrophic 3T3-L1 adipocyte model by immunofluorescence microscopy. Four compounds of 29 total compounds have been tentatively identified in L. citriodora for the first time by HPLC-ESI-TOF-MS. Phenylpropanoids (verbascoside), iridoids (gardoside) and flavonoids (luteolin-7-diglucoronide) were the best candidates to account for activating AMPK capacity. The combination of specific polyphenols from L. citriodora , which showed strong activating AMPK capacity, could be an alternative in the management of obesity-associated diseases. [ABSTRACT FROM AUTHOR]