Entry #: 49
Date: 29 April 2018
Section: Phenolic compounds
Topic: Oleacein and insulin resistance
Type: In vivo model

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D. Elizabeth McCord, Nancy B. Ray and Tom C. Karagiannis


Effects of oleacein on high-fat diet-dependent steatosis, weight gain, and insulin resistance in mice


Lombardo et al

Citation / Year

(1) / 2018


Extra-virgin olive oil, oleuropein, oleacein, high-fat diet, obesity, liver steatosis, plasma glucose, insulin resistance


Metabolic diseases including obesity, metabolic syndrome, and diabetes represent major clinical problems which are anticipated to rise in coming years (2). One of the major underlying pathologies, is insulin resistance, resulting in higher the average blood glucose levels (3). Physical activity, and changes in dietary patterns have been in associated with improvements in various metabolic disorders, and in particular the Mediterranean diet with a high consumption of extra-virgin olive oil has been shown to be beneficial (4, 5). Research has indicated that the minor phenolic component of extra-virgin olive oil is largely responsible for the beneficial effects (6). Hydroxytyrosol and oleuropein have been the most widely investigated, and beneficial effects in cell culture, in vivo models, and in limited human trials have been observed (7, 8). In this study the authors investigated both oleuropein, and its degradation product oleacein. Oleacein has been shown to have a favourable bioavailability profile, and has recently been shown to have beneficial effects in models of ischemia and cardiovascular disease (9-12). In this study, the effects oleacein on metabolic parameters in mice fed a high-fat diet was investigated; oleuropein was also used in the first series of experiments.

Key points and implications

In these experiments the C57BL/6JOlaHsd mouse strain, which susceptible to diabetes and diet-induced obesity was used. For the first set of experiments, male mice (n=28), were divided into four groups: 1) normocaloric diet (n=8), 2) high-fat diet (n=12), 3) high-fat diet with 20 mg/kg oleacein (daily, oral gavage, n=4), and 4) high-fat diet with 20 mg/kg oleuropein (daily, oral gavage, n=4). The experiment was performed over a five week period. In the second set of experiments, at the end of the five week period, the mice from the high-fat diet group were divided into two groups and either: 1) continued to receive the high-fat diet (n=4), or 2) received a high-fat diet with 20 mg/kg oleacein (daily, oral gavage, n=4), for a further eight weeks. Therefore, analyses were performed at week five and week 13. In summary the key findings indicated: 1) both oleuropein and oleacein decreased visceral fat and body weight compared to the high-fat fed animals, 2) oleuropein and oleacein attenuated high-fat diet-induced changes in biochemical parameters including, plasma glucose levels, insulin levels, insulin sensitivity, and total cholesterol, 3) oleuropein and oleacein prevented high-fat diet-induced liver enlargement and steatosis with decreases in the expression of SREBP-1, FAS, and p-ERK, and 4) the effects of oleacein in established disease (obesity; 13 week end-point), were less pronounced, indicating that oleacein may have more utility in prevention. Overall, these findings re-iterate and highlight the potential beneficial effects of olive phenolics in counteracting metabolic aberrations associated with obesity and insulin resistance. Further work is necessary to further clarify these findings and to determine applicability as appropriate dietary intervention in humans.

Related publications

  1. G. E. Lombardo et al., Effects of Oleacein on High-Fat Diet-Dependent Steatosis, Weight Gain, and Insulin Resistance in Mice. Frontiers in endocrinology 9, 116 (2018).
  2. M. Agha, R. Agha, The rising prevalence of obesity: part A: impact on public health. International journal of surgery. Oncology 2, e17 (2017).
  3. S. E. Kahn, R. L. Hull, K. M. Utzschneider, Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444, 840-846 (2006).
  4. P. M. Mutie, G. N. Giordano, P. W. Franks, Lifestyle precision medicine: the next generation in type 2 diabetes prevention? BMC medicine 15, 171 (2017).
  5. M. Greco et al., Early effects of a hypocaloric, Mediterranean diet on laboratory parameters in obese individuals. Mediators of inflammation 2014, 750860 (2014).
  6. S. Cicerale, L. Lucas, R. Keast, Biological activities of phenolic compounds present in virgin olive oil. International journal of molecular sciences 11, 458-479 (2010).
  7. S. Bulotta et al., Beneficial effects of the olive oil phenolic components oleuropein and hydroxytyrosol: focus on protection against cardiovascular and metabolic diseases. Journal of translational medicine 12, 219 (2014).
  8. B. Barbaro et al., Effects of the olive-derived polyphenol oleuropein on human health. International journal of molecular sciences 15, 18508-18524 (2014).
  9. P. Costanzo et al., Simple and efficient sustainable semi-synthesis of oleacein [2-(3,4-hydroxyphenyl) ethyl (3S,4E)-4-formyl-3-(2-oxoethyl)hex-4-enoate] as potential additive for edible oils. Food chemistry 245, 410-414 (2018).
  10. M. Nardi et al., Biomimetic synthesis and antioxidant evaluation of 3,4-DHPEA-EDA [2-(3,4-hydroxyphenyl) ethyl (3S,4E)-4-formyl-3-(2-oxoethyl)hex-4-enoate]. Food chemistry 162, 89-93 (2014).
  11. A. Filipek, M. E. Czerwinska, A. K. Kiss, M. Wrzosek, M. Naruszewicz, Oleacein enhances anti-inflammatory activity of human macrophages by increasing CD163 receptor expression. Phytomedicine : international journal of phytotherapy and phytopharmacology 22, 1255-1261 (2015).
  12. M. Naruszewicz, M. E. Czerwinska, A. K. Kiss, Oleacein. translation from Mediterranean diet to potential antiatherosclerotic drug. Current pharmaceutical design 21, 1205-1212 (2015).