Effect of Oleuropein on Anti-Obesity and Uncoupling Protein 1 Level in Brown Adipose Tissue in Mild Treadmill Walking Rats with Diet-Induced Obesity.

Oleuropein aglycone (OA), which is the absorbed form of oleuropein, is a major phenolic compound in extra virgin olive oil. We analyzed the anti-obesity effect of OA intake combined with mild treadmill walking (MTW, 4 m/min for 20 min/d, 5-6 d/wk, without electric shocks and slope) in rats under a high-fat diet (HF). Four-week-old male Sprague-Dawley rats (n=28) were equally divided into four groups: control (HF), 0.08% oleuropein-supplemented HF (HFO), HF with MTW (HF+W), and HFO with MTW (HFO+W) groups. After 28 d, the inguinal subcutaneous fat content and weight gain were significantly lower in the HFO+W group than in the control group. The HFO+W group also had significantly higher levels of urinary noradrenaline secretion, interscapular brown adipose tissue, uncoupling protein 1, brain transient receptor potential ankyrin subtype 1 (TRPA1), vanilloid subtype 1 (TRPV1), and brain-derived neurotrophic factor (BDNF) than the control group. Especially, the HFO+W group showed a synergistic effect on noradrenaline secretion. Therefore, OA combined with MTW may accelerate the enhancement of UCP1 and BDNF levels in rats with HF-induced obesity by increasing noradrenaline secretion after TRPA1 and TRPV1 activation.

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

Oleuropein is the pungent principle of raw olives. Oleuropein aglycone (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 oleuropein and OA on interscapular brown adipose tissue (IBAT) in rats with high-fat (HF) diet-induced obesity by examining the agonistic activity of oleuropein and OA toward the transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (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 TRPV1 antagonist and by a ß2- or ß3-adrenoceptor antagonist. Furthermore, OA-activated rat and human TRPV1s expressed 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 TRPV1 and that OA enhances UCP1 expression in IBAT with a concomitant decrease in the visceral fat mass of HF-diet-induced obese rats through enhanced noradrenaline secretion via ß-adrenergic action following TRPA1 and TRPV1 activation.

Oleuropein supplementation increases urinary noradrenaline and testicular testosterone levels and decreases plasma corticosterone level in rats fed high-protein diet.

The effects of oleuropein, a phenolic compound in extra virgin olive oil, on protein metabolism were investigated by measuring testicular testosterone and plasma corticosterone levels in rats fed diets with different protein levels. In Experiment 1, rats were fed experimental diets with different protein levels (40, 25 and 10 g/100 g casein) with or without 0.1 g/100 g oleuropein. After 28 days of feeding, the testosterone level in the testis was significantly higher and the plasma corticosterone level was significantly lower in rats fed the 40% casein diet with oleuropein than in those fed the same diet without oleuropein. The urinary noradrenaline level, nitrogen balance and hepatic arginase activity were significantly higher in rats fed the 40% casein diet with oleuropein supplementation than in those fed the 40% casein diet without oleuropein supplementation. In Experiment 2, the effects of oleuropein aglycone (a major phenolic compound in extra virgin olive oil and the absorbed form of oleuropein ingested in the gastrointestinal tracts) on the secretion of luteinizing hormone (LH) from the pituitary gland, which regulates testosterone production in the testis, were investigated in anesthetized rats. Plasma LH level increased dose dependently after the administration of oleuropein aglycone (P<.001, r=0.691). These findings suggest that dietary supplementation with 0.1 g/100 g oleuropein alters the levels of hormones associated with protein anabolism by increasing urinary noradrenaline and testicular testosterone levels and decreasing plasma corticosterone level in rats fed a high-protein diet.

Oleuropein, a phenolic compound in extra virgin olive oil, increases uncoupling protein 1 content in brown adipose tissue and enhances noradrenaline and adrenaline secretions in rats.

The effects of oleuropein, a phenolic compound in extra virgin olive oil (EV-olive oil), on triglyceride metabolism were investigated by measuring the degree of thermogenesis in interscapular brown adipose tissue (IBAT), and noradrenaline and adrenaline secretions in rats. In Experiment 1, rats were given a high-fat diet (control diet) with the oleuropein supplementation of 1, 2 or 4 mg/kg of diet (0.1, 0.2 or 0.4% oleuropein diet, respectively). After 28 d of feeding, body weight, perirenal adipose tissue, epididymal fat pad, and plasma triglyceride, free fatty acid and total cholesterol concentrations were reduced by the 0.1, 0.2 or 0.4% oleuropein diet and were significantly lowest in rats fed the 0.4% oleuropein diet, as compared with those of rats fed with the control diet. The content of uncoupling protein 1 (UCP1) in IBAT and urinary noradrenaline and adrenaline excretions were significantly higher in rats fed the 0.1 or 0.2% oleuropein diet, as compared with those of rats fed with the control diet, although there were no significant differences in rats fed the 0.4% oleuropein diet. In Experiment 2, the effects of oleuropein on noradrenaline and adrenaline secretion were evaluated. The intravenous administration of oleuropein and oleuropein aglycone significantly increased plasma noradrenaline and adrenaline concentrations. Furthermore, oleuropein aglycone induced the secretions of noradrenaline and adrenaline about ten fold more potently than oleuropein. These results suggest that the phenolic compound oleuropein in EV-olive oil enhances thermogenesis by increasing the UCP1 content in IBAT and noradrenaline and adrenaline secretions in rats.

Extra virgin olive oil increases uncoupling protein 1 content in brown adipose tissue and enhances noradrenaline and adrenaline secretions in rats.

The effects of extra virgin olive oil (EV-olive oil) on triglyceride metabolism were investigated by measuring the degree of thermogenesis in interscapular brown adipose tissue (IBAT) and the rates of noradrenaline and adrenaline secretions in rats, both in vivo and in situ. In Experiment 1 (in vivo), rats were given an isoenergetic high-fat diet (30% fat diet) containing corn oil, refined olive oil, or EV-olive oil. After 28 days of feeding, the final body weight, weight gain, energy efficiency, perirenal adipose tissue and epididymal fat pad and plasma triglyceride concentrations were the lowest in the rats fed the EV-olive oil diet. The content of uncoupling protein 1 (UCP1) in IBAT and the rates of urinary noradrenaline and adrenaline excretions were the highest in the rats fed the EV-olive oil diet. In Experiment 2 (in situ), the effects of the extract of the phenolic fraction from EV-olive oil and a compound having excellent characteristics as components of EV-olive oil, hydroxytyrosol, on noradrenaline and adrenaline secretions were evaluated. The intravenous administration of the extract of the phenolic fraction from EV-olive oil significantly increased plasma noradrenaline and adrenaline concentrations, whereas that of hydroxytyrosol had no effect. These results suggest that phenols except hydroxytyrosol in EV-olive oil enhance thermogenesis by increasing the UCP1 content in IBAT and enhancing noradrenaline and adrenaline secretions in rats.