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

Abstract

Inflammation of the adipose tissue plays an important role in the development of several chronic diseases associated with obesity. Polyphenols of extra virgin olive oil (EVOO), such as the secoiridoids oleocanthal (OC) and oleacein (OA), have many nutraceutical proprieties. However, their roles in obesity-associated adipocyte inflammation, the NF-κB pathway and related sub-networks have not been fully elucidated. Here, we investigated impact of OC and OA on the activation of NF-κB and the expression of molecules associated with inflammatory and dysmetabolic responses. To this aim, fully differentiated Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were pre-treated with OC or OA before stimulation with TNF-α. EVOO polyphenols significantly reduced the expression of genes implicated in adipocyte inflammation (IL-1β, COX-2), angiogenesis (VEGF/KDR, MMP-2), oxidative stress (NADPH oxidase), antioxidant enzymes (SOD and GPX), leukocytes chemotaxis and infiltration (MCP-1, CXCL-10, MCS-F), and improved the expression of the anti-inflammatory/metabolic effector PPARγ. Accordingly, miR-155-5p, miR-34a-5p and let-7c-5p, tightly connected with the NF-κB pathway, were deregulated by TNF-α in both cells and exosomes. The miRNA modulation and NF-κB activation by TNF-α was significantly counteracted by EVOO polyphenols. Computational studies suggested a potential direct interaction between OC and NF-κB at the basis of its activity. This study demonstrates that OC and OA counteract adipocyte inflammation attenuating NF-κB activation. Therefore, these compounds could be novel dietary tools for the prevention of inflammatory diseases associated with obesity.

Daily Use of Extra Virgin Olive Oil with High Oleocanthal Concentration Reduced Body Weight, Waist Circumference, Alanine Transaminase, Inflammatory Cytokines and Hepatic Steatosis in Subjects with the Metabolic Syndrome: A 2-Month Intervention Study

“…This data suggests that the consumption of EVOO with a high content of OC can have important anti-inflammatory effects, and it is consistent with the natural anti-inflammatory properties of OC [ 14 , 77 , 78 ]. It has been previously reported that one of the mechanisms underlying the anti-inflammatory properties of OC is the inhibition of the nuclear factor-κB (NF-kB) pathway [ 79 ], which in turn may not only reduce the levels of pro-inflammatory cytokines but also attenuate cortical cyclooxygenase-2 (COX-2) signaling [ 80 ]. However, further investigations are needed for a better understanding of this aspect.…”

Do Olive and Fish Oils of the Mediterranean Diet Have a Role in Triple Negative Breast Cancer Prevention and Therapy? An Exploration of Evidence in Cells and Animal Models

“…Stromal overexpression of COX2 has also been shown to be an independent indicator of worse overall survival in breast cancer ( 133 ). Oleocanthal has demonstrated the capacity to downregulate expression of COX2 and activity of NF-kB in adipocytes ( 134 ). Given that the breast stroma is largely populated by adipocytes, this collective evidence suggests the MD could facilitate an intra- and extra-tumoral environment that suppresses the NF-κB/COX2 pathway.…”

Diet to Reduce the Metabolic Syndrome Associated with Menopause. The Logic for Olive Oil

“…Considerable antioxidant and anti-inflammatory potential has also been exhibited by oleocanthal, a phenolic compound responsible for the burning sensation at the back of the throat when consuming EVOO [ 81 , 82 ], and by other phenolic compounds [ 83 , 84 ].…”