Oleuropein aglycone enhances UCP1 expression in brown adipose tissue in high-fat-diet-induced obese rats by activating β-adrenergic signaling☆☆☆★

Abstract Oleuropeinis the pungent principle of raw olives. Oleuropeinaglycone (OA) is a major phenolic compound in extra virgin olive oil and the absorbed form of oleuropein. We aimed to determine the mechanism underlying the nutritional effects of oleuropeinand OA on interscapular brown adipose tissue(IBAT) in rats with high-fat (HF) diet-induced obesityby examining the agonistic activity of oleuropeinand OA toward the transient receptor potential ankyrin1 (TRPA1) and vanilloid1 ( TRPV1). Four-week-old male Sprague–Dawley rats were fed an HF (palm oil 30% wt:wt) diet alone or with oleuropein(HF-O, 1 g/kg diet) for 28 days. In rats fed HF-O compared to HF, urinary noradrenaline, adrenaline and UCP1 levels in IBAT were significantly higher, whereas plasma leptin levels and the total weight of the abdominal cavity adipose tissue were significantly lower. In anaesthetized 7-week-old male Sprague–Dawley rats, the OA (3.8 mg of intravenous injection)-induced increase in plasma noradrenaline secretion was suppressed by TRPA1 or TRPV1antagonist and by a β2- or β3-adrenoceptor antagonist. Furthermore, OA-activated rat and human TRPV1sexpressed on HEK293 cells at the same level as zingerone(pungent component in ginger). OA also activated humanTRPA1, and its potency was approximately 10-fold stronger than that for TRPV1. These findings suggest that OA is the agonist of both TRPA1 and TRPV1and that OA enhances UCP1 expression in IBAT with a concomitant decrease in the visceral fat mass of HF- diet-induced obeserats through enhanced noradrenaline secretion via β-adrenergic action following TRPA1 and TRPV1activation.