oleuropein and Obesity

Cancer cells exhibit enhanced proliferation rate and a resistance to apoptosis. Epidemiological studies suggest that olive oil intake is associated with a reduced risk of cancer. Olive oil, olives, and olive leaves contain many polyphenols, including oleuropein. Recently, several studies have demonstrated that oleuropein inhibits proliferation and induces apoptosis in different cancer cell lines. In addition, anticancer effects of oleuropein have been seen in animal studies. These effects are associated with oleuropein's ability to modulate gene expression and activity of a variety of different signaling proteins that play a role in proliferation and apoptosis. This article summarizes the existing in vitro and in vivo studies focusing on the anticancer effects of oleuropein and its effects on key signaling molecules. © 2017 BioFactors, 43(4):517-528, 2017.

Topics: Animals; Anthocyanins; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Proliferation; Humans; Iridoid Glucosides; Iridoids; Obesity

Diet-induced obesity models are widely used to investigate dietary interventions for treating obesity. This study was aimed to test whether a dietary intervention based on a calorie-restricted cafeteria diet (CAF-R) and a polyphenolic compound (Oleuropein, OLE) supplementation modified sucrose intake, preference, and taste reactivity in cafeteria diet (CAF)-induced obese rats. CAF diet consists of high-energy, highly palatable human foods. Male rats fed standard chow (STD) or CAF diet were compared with obese rats fed CAF-R diet, alone or supplemented with an olive tree leaves extract (25 mg/kg*day) containing a 20.1% of OLE (CAF-RO). Biometric, food consumption, and serum parameters were measured. CAF diet increased body weight, food and energy consumption and obesity-associated metabolic parameters. CAF-R and CAF-RO diets significantly attenuated body weight gain and BMI, diminished food and energy intake and improved biochemical parameters such as triacylglycerides and insulin resistance which did not differ between CAF-RO and STD groups. The three cafeteria groups diminished sucrose intake and preference compared to STD group. CAF-RO also diminished the hedonic responses for the high sucrose concentrations compared with the other groups. These results indicate that CAF-R diet may be an efficient strategy to restore obesity-associated alterations, whilst OLE supplementation seems to have an additional beneficial effect on sweet taste function.

Topics: Animals; Anti-Infective Agents; Behavior, Animal; Caloric Restriction; Dietary Supplements; Dose-Response Relationship, Drug; Eating; Energy Metabolism; Iridoid Glucosides; Male; Obesity; Rats; Rats, Sprague-Dawley; Sucrose

Obesity is a risk factor for development of metabolic diseases and cognitive decline; therefore, obesity prevention is of paramount importance. Neuronal mitochondrial dysfunction induced by oxidative stress is an important mechanism underlying cognitive decline. Olive leaf extract contains large amounts of oleanolic acid, a transmembrane G protein-coupled receptor 5 (TGR5) agonist, and oleuropein, an antioxidant. Activation of TGR5 results in enhanced mitochondrial biogenesis, which suggests that olive leaf extract may help prevent cognitive decline through its mitochondrial and antioxidant effects. Therefore, we investigated olive leaf extract's effects on obesity, cognitive decline, depression, and endurance exercise capacity in a mouse model. In physically inactive mice fed a high-fat diet, olive leaf extract administration suppressed increases in fat mass and body weight and prevented cognitive declines, specifically decreased working memory and depressive behaviors. Additionally, olive leaf extract increased endurance exercise capacity under atmospheric and hypoxic conditions. Our study suggests that these promising effects may be related to oleanolic acid's improvement of mitochondrial function and oleuropein's increase of antioxidant capacity.

Topics: Animals; Cognitive Dysfunction; Depression; Diet, High-Fat; Disease Models, Animal; Exercise Tolerance; Humans; Iridoid Glucosides; Male; Mice; Mitochondria; Obesity; Olea; Oleanolic Acid; Oxidative Stress; Physical Conditioning, Animal; Plant Extracts; Plant Leaves; Receptors, G-Protein-Coupled

Topics: Animals; Beverages; Chromatography, Liquid; Diet, High-Fat; Gas Chromatography-Mass Spectrometry; Hyperlipidemias; Iridoid Glucosides; Iridoids; Male; Mice; Mice, Inbred ICR; Obesity; Olea; Phenylethyl Alcohol; Plant Leaves; Tandem Mass Spectrometry

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 β2- or β3-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 β-adrenergic action following TRPA1 and TRPV1 activation.

Topics: Acetates; Adipose Tissue, Brown; Animals; Catecholamines; Cyclopentane Monoterpenes; Diet, High-Fat; Epinephrine; HEK293 Cells; Humans; Iridoid Glucosides; Iridoids; Male; Norepinephrine; Obesity; Pyrans; Rats, Sprague-Dawley; Signal Transduction; TRPA1 Cation Channel; TRPV Cation Channels; Uncoupling Protein 1

Oleuropein, which is the major compound of olive leaves, has been reported to exert several pharmacological properties, including anti-cancer, antidiabetic and anti-atherosclerotic activities. The objective of this study was to evaluate the effect of oleuropein on adiponectin level in high cholesterol diet (HCD) induced obesity in rat and the molecular mechanism underlying its activation. Our results showed that orally administered oleuropein (50 mg/kg) by gavage for 8 weeks decreased the body weight, adipose tissue mass and triglyceride and attenuated steatosis in liver. Moreover, the effect of oleuropein on adiponectin, an important hormone with fatty-acid oxidation properties, was evaluated and our data illustrated that oleuropein supplementation increased serum adiponectin concentration. The effects of oleuropein on protein expression related to lipogenic genes were investigated and our results showed that its administration significantly inhibited peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein-1c (SREBP-1c) and fatty-acid synthase (FAS). In addition, oleuropein stimulated the HCD-induced inhibition of AMP-activated protein kinase (AMPK) in epididymal adipose tissues. These results suggest that oleuropein exerts anti-obesity effects in HCD rats by activating AMPK and suppressing PPAR γ (Peroxisome proliferator-activated receptor γ) expression in adipose tissues. These data provide that oleuropein has important implications for preventing obesity.

Topics: Adiponectin; AMP-Activated Protein Kinases; Animals; Anti-Obesity Agents; Anticholesteremic Agents; Cholesterol; Enzyme Activation; Iridoid Glucosides; Iridoids; Lipid Metabolism; Lipids; Male; Obesity; PPAR gamma; Rats; Rats, Wistar; Sterol Regulatory Element Binding Protein 1

Olive oil and its minor constituents have been recommended as important dietary therapeutic interventions in preventive medicine. However, a question remains to be addressed: what are the effects of olive oil and its phenolic compounds on obesity-induced cardiac metabolic changes?. Male Wistar rats were divided into two groups (n = 24/group): (C) receiving standard-chow; (Ob) receiving hypercaloric-chow. After 21 days C and Ob groups were divided into four subgroups (n = 6/group):(C) standard-chow and saline; (C-Olive)standard-chow and olive-oil (3.0 g/kg.day); (C-Oleuropein)standard-chow and oleuropein (0.023 mg/kg/day); (C-Cafeic) standard-chow and cafeic-acid (2.66 mg/kg/day); (Ob)receiving hypercaloric-chow and saline;(Ob-Olive) hypercaloric-chow and olive-oil;(Ob-Oleuropein) hypercaloric-chow and oleuropein;(Ob-Cafeic) hypercaloric-chow and cafeic-acid. Treatments were given twice a week during 21 days.. After 42 days, obesity was evidenced in Ob rats from enhanced body-weight, surface-area, and body-mass-index. Energy-expenditure, oxygen consumption(VO2) and fat-oxidation were lower in Ob-group than in C. Despite no morphometric changes, Ob-Olive, Ob-Oleuropein and Ob-Cafeic groups had higher VO2, fat-oxidation, myocardial beta-hydroxyacyl coenzyme-A dehydrogenase and lower respiratory-quotient than Ob. Citrate-synthase was highest in Ob-Olive group. Myocardial lipid-hydroperoxide(LH) and antioxidant enzymes were unaffected by olive-oil and its compounds in obesity condition, whereas LH was lower and total-antioxidant-substances were higher in C-Olive and C-Oleuropein than in C.. The present study demonstrated for the first time that olive-oil, oleuropein and cafeic-acid enhanced fat-oxidation and optimized cardiac energy metabolism in obesity conditions. Olive oil and its phenolic compounds improved myocardial oxidative stress in standard-fed conditions.

Topics: 3-Hydroxyacyl CoA Dehydrogenases; Animals; Caffeic Acids; Calorimetry; Citrate (si)-Synthase; Iridoid Glucosides; Iridoids; Male; Myocardium; Obesity; Olive Oil; Phenols; Plant Oils; Pyrans; Rats; Rats, Wistar