Effects of Oleacein on High-Fat Diet-Dependent Steatosis, Weight Gain, and Insulin Resistance in Mice

Abstract

Many reports indicate that the protective action of nutraceuticals in the Mediterranean diet, against metabolic and cardiovascular diseases, can be attributed to the action of polyphenolic components of extra-virgin olive oil (EVOO). Here, we evaluated the protective effects of oleacein, one of the most abundant secoiridoids in EVOO, on the damages/metabolic alterations caused by high-fat diet (HFD) in male C57BL/6JolaHsd mice. After 5 weeks of treatment with 20 mg/kg of oleacein, body weight, glycemia, insulinemia, serum lipids, and histologic examination of liver tissue indicated a protective action of oleacein against abdominal fat accumulation, weight gain, and liver steatosis, with improvement of insulin-dependent glucose and lipid metabolism. Both serum parameters and hepatic histologic examination were altered in mice fed with HFD. By contrast, in the animals that received oleacein, plasma glucose, cholesterol and triglyceride serum levels, and liver histology were similar to controls fed with normocaloric diet. In addition, protein levels of FAS, SREBP-1, and phospho-ERK in liver were positively modulated by oleacein, indicating an improvement in liver insulin sensitivity. In a group of obese mice, treatment with oleacein determined a light, but still significant reduction of the increase in body weight, mainly due to lesser liver steatosis enlargement, associated with reduced levels of SREBP-1 and phospho-ERK and lower levels of total serum cholesterol; in these animals, altered plasma glucose and triglyceride serum levels were not reverted by oleacein. These results indicate that HFD-related hepatic insulin resistance may be partially prevented by oral administration of oleacein, suggesting a protective role of this nutraceutical against diet-dependent metabolic alterations. Additional studies are necessary to check whether oleacein can be used as an adjuvant to improve insulin sensitivity in humans.

Mediterranean Diet Nutrients to Turn the Tide against Insulin Resistance and Related Diseases

“…Several studies, in this context, have investigated the biological activities of polyphenolic compounds in EVOO, such as oleuropein and its derivative secoiridoids, either in vitro or in vivo, in experimental animal models [81][82][83][84]. Recently, it has been given importance to oleacein, an abundant lipophilic degradation product of oleuropein, present in EVOO at higher concentration and provided with an increased bioavailability, due to higher resistance to the acidic gastric environment and better intestinal absorption [85]. Additionally, the semi-synthesis of oleacein has proven to be sustainable [86], laying the foundation for the future implementation of novel functional foods and nutraceuticals.…”

“…Although this concept is still at early developmental stages, mice on high fat diet (HFD), treated with 20 mg/day oleacein for 5 weeks, were protected from abdominal fat accumulation, weight gain, and liver steatosis when compared to untreated controls, with evidence of improved insulin action on the liver and preserved glucose and lipid homeostasis [87]. Some of the molecular constituents, that appear to be involved in oleacein action, include some known nutrient-responsive regulators of lipid metabolism: the transcriptional activator sterol regulatory element-binding transcription factor-1 (SREBP-1), and its target fatty acid synthase (FAS), whose protein levels were significantly reduced following oleacein treatment in liver and fat [85,87]. Also, phospho-ERK, a serine/threonine kinase downstream effector of the mitogen-activated protein kinase (MAPK) cascade, was inhibited in liver tissue of treated mice, thereby suggesting greater responsiveness to insulin and less severity of IR, in situations of chronic high-fat hypernutrition [88].…”

The Extra-Virgin Olive Oil Polyphenols Oleocanthal and Oleacein Counteract Inflammation-Related Gene and miRNA Expression in Adipocytes by Attenuating NF-κB Activation

“…Data concerning the action of EVOO polyphenols in the context of human obesity-related AT inflammation and dysfunction are scarce, and mainly regard oleuropein and its derivative hydroxytyrosol, demonstrating potential anti-obesity and anti-diabetic effect [42][43][44][45][46]. Recently, beneficial properties of in vivo administration of OA have been reported, showing protective effects against weight gain, insulin resistance, liver steatosis, and lipid metabolism in high fat diet-fed mice [47]. Data on the effect of OC and OA on obesity-associated inflammatory responses in adipocytes are lacking.…”

Oleacein and Foam Cell Formation in Human Monocyte-Derived Macrophages: A Potential Strategy against Early and Advanced Atherosclerotic Lesions

“…This effect has been related to decreased expression of macrophages receptors, such as SRA, CD36 and LOX-1. Moreover, in an animal model, oleacein may have attenuated foam cell formation in the livers of mice [25].…”

“…Nevertheless, current in vivo studies support our hypothesis that oleacein may prevent the accumulation of cholesterol in mouse liver macrophages. [25].…”