Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Apr 12;14(8):1606.
doi: 10.3390/nu14081606.

Molecular Mechanisms Underlying the Effects of Olive Oil Triterpenic Acids in Obesity and Related Diseases

Carmen M Claro-Cala  1 , Francesc Jiménez-Altayó  2 , Sebastián Zagmutt  3 , Rosalia Rodriguez-Rodriguez  3
Affiliations
Review

Molecular Mechanisms Underlying the Effects of Olive Oil Triterpenic Acids in Obesity and Related Diseases

Carmen M Claro-Cala et al. Nutrients. .

Abstract

Dietary components exert protective effects against obesity and related metabolic and cardiovascular disturbances by interfering with the molecular pathways leading to these pathologies. Dietary biomolecules are currently promising strategies to help in the management of obesity and metabolic syndrome, which are still unmet medical issues. Olive oil, a key component of the Mediterranean diet, provides an exceptional lipid matrix highly rich in bioactive molecules. Among them, the pentacyclic triterpenic acids (i.e., oleanolic acid) have gained clinical relevance in the last decade due to their wide range of biological actions, particularly in terms of vascular function, obesity and insulin resistance. Considering the promising effects of these triterpenic compounds as nutraceuticals and components of functional foods against obesity and associated complications, the aim of our review is to decipher and discuss the main molecular mechanisms underlying these effects driven by olive oil triterpenes, in particular by oleanolic acid. Special attention is paid to their signaling and _targets related to glucose and insulin homeostasis, lipid metabolism, adiposity and cardiovascular dysfunction in obesity. Our study is aimed at providing a better understanding of the impact of dietary components of olive oil in the long-term management of obesity and metabolic syndrome in humans.

Keywords: adiposity; insulin resistance; obesity; oleanolic acid; olive oil; triterpenes; vascular diseases.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structures of most important triterpenic acids and alcohols in olive oil.
Figure 2
Figure 2
Key actions of insulin under healthy or obesity conditions in central and peripheral tissues in response to diet and the beneficial effects of oleanolic acid. In healthy individuals (black letters), insulin is released in response to diet, leading to glucose uptake in the muscle, hepatic production of glucose and glycogen, and attenuation of lipolysis in white adipose tissue and food intake reduction. These mechanisms are disrupted in obesity and type 2 diabetes (T2D) driving insulin resistance (red letters) with glucose uptake attenuation, increased lipolysis and hepatic production of glucose. In green letters are indicated the main actions and _targets by which oleanolic acid is improving insulin sensitivity in obesity, thorough the promotion of glucose transporter translocation in muscle cells, reduction of ectopic fat accumulation, restoration of IRS-, PPAR- and mTOR-dependent pathways, ROS and inflammation in metabolically active tissues in the periphery. ROS, reactive oxygen species; GLUT4, glucose transporter type 4; LPL, lipoprotein lipase; HSL, hormone-sensitive lipase; IRS-1, insulin receptor substrate 1; PI3K, phosphoinositide 3-kinases; Akt, protein kinase B; PPARγ/α, peroxisome proliferator-activated receptor gamma/alpha; IRS-1, insulin receptor substrate 1; Mitoch., Mitochondrial; mTOR, mammalian _target of rapamycin; CREB, cyclic adenosine monophosphate (cAMP)-response element binding protein; ↓, decrease; ↑, increase.
Figure 3
Figure 3
Effects of triterpenic acids on lipid homeostasis and adiposity in liver and white adipose tissue and in brain cells. In the liver, oleanolic acid inhibits the expression of SREBP1-responsive genes and promotes the expression of PPARα leading to anti-inflammatory effects in animal models of obesity. In the adipose tissue, oleanolic and maslinic acids interfere in different steps of adipogenesis and lipolysis by down-regulation of the expression of C/EBPα and PPARγ, and by modulating anti-adipogenic pathways and kinases (MAPK, AMPK, and cAMP-dependent PKA). Oleanolic acid also attenuates inflammation in adipose tissue by diverting macrophage infiltration and polarization to the anti-inflammatory M2 phenotype. SREBP1, sterol regulatory element-binding protein 1; SREBP1c, sterol regulatory element-binding protein-1c; SRE, sterol regulatory element; Scd1, stearoyl coenzyme A desaturase 1; Fas, fatty acid synthase; Acc, acetyl-coenzyme A carboxylase; AC, adenylyl cyclase; cAMP, cyclic adenosine monophosphate; PKA, protein kinase A; MAPK, mitogen-activated protein kinases; AMPK, adenosine monophosphate activated protein kinase; Ca2+, calcium ions; C/EBPα, cytosine-cytosine-adenosine-adenosine-thymidine (CCAAT) enhancer-binding protein alpha; M1 and M2, phenotype macrophages; IL-6, interleukin 6; iNOS, inducible nitric oxide synthase; TNFα, tumor necrosis factor alpha; ARG1, arginase 1; IL10, interleukin 10; MRC1, mannose receptor C-type 1.
Figure 4
Figure 4
Main mechanisms involved in the beneficial vascular effects of triterpenic acids. Vasodilation evoked by oleanolic acid implies endothelium-dependent and independent pathways. In the endothelium, oleanolic acid induces PI3K-dependent phosphorylation of Akt-Ser (473) followed by phosphorylation of eNOS-Ser (1177) with subsequent release of nitric oxide (NO) and PPARδ activation. In the vascular smooth muscle, oleanolic acid leads to vasodilation throughout activation of ATP-dependent and voltage-activated K+ channels and by induction of prostacyclin (PGI2) release after COX-2 activation. P, phosphorylation; eNOS, endothelial NO synthase; PPARδ, peroxisome proliferator-activated receptor delta; Pdk4, pyruvate dehydrogenase kinase 4; Plin2, perilipin 2; Angptl4, angiopoietin like 4; Kv, voltage-gated potassium channel; KATP, adenosine 5’-triphosphate (ATP)-sensitive potassium; COX-2, cyclooxygenase-2; Ser, serine.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. World Health Organization Obesity and Overweight. [(accessed on 19 November 2019)]. Available online: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
    1. Nyberg S.T., Batty G.D., Pentti J., Virtanen M., Alfredsson L., Fransson E.I., Goldberg M., Heikkilä K., Jokela M., Knutsson A., et al. Obesity and loss of disease-free years owing to major non-communicable diseases: A multicohort study. Lancet Public Health. 2018;3:e490–e497. doi: 10.1016/S2468-2667(18)30139-7. - DOI - PMC - PubMed
    1. Kluge H.H.P., Wickramasinghe K., Rippin H.L., Mendes R., Peters D.H., Kontsevaya A., Breda J. Prevention and control of non-communicable diseases in the COVID-19 response. Lancet. 2020;395:1678–1680. doi: 10.1016/S0140-6736(20)31067-9. - DOI - PMC - PubMed
    1. Pineda E., Sanchez-Romero L.M., Brown M., Jaccard A., Jewell J., Galea G., Webber L., Breda J. Forecasting Future Trends in Obesity across Europe: The Value of Improving Surveillance. Obes. Facts. 2018;11:360–371. doi: 10.1159/000492115. - DOI - PMC - PubMed
    1. Grosso G., Mistretta A., Marventano S., Purrello A., Vitaglione P., Calabrese G., Drago F., Galvano F. Beneficial effects of the Mediterranean diet on metabolic syndrome. Curr. Pharm. Des. 2014;20:5039–5044. doi: 10.2174/1381612819666131206112144. - DOI - PubMed
  NODES
Association 1
INTERN 2
twitter 2