Hydroxytyrosol in the Prevention of the Metabolic Syndrome and Related Disorders

Abstract

Virgin olive oil (VOO) constitutes the main source of fat in the Mediterranean diet. VOO is rich in oleic acid, displaying health-promoting properties, but also contains minor bioactive components, especially phenolic compounds. Hydroxytyrosol (HT), the main polyphenol of olive oil, has been reported to be the most bioactive component. This review aims to compile the results of clinical, animal and cell culture studies evaluating the effects of HT on the features of Metabolic Syndrome (MetS) (body weight/adiposity, dyslipidemia, hypertension, and hyperglycemia/insulin resistance) and associated complications (oxidative stress and inflammation). HT was able to improve the lipid profile, glycaemia, and insulin sensitivity, and counteract oxidative and inflammatory processes. Experimental studies identified multiple molecular targets for HT conferring its beneficial effect on health in spite of its low bioavailability. However, rodent experiments and clinical trials with pure HT at biologically relevant concentrations are still lacking. Moreover, the roles of intestine and its gut microbiota have not been elucidated.

Docosahexaenoic acid and hydroxytyrosol co‐administration fully prevents liver steatosis and related parameters in mice subjected to high‐fat diet: A molecular approach

“…Data presented using mice fed a HFD for 12 weeks show significant decreases ( p < .05) in NF‐κB up‐regulation and NF‐κB‐dependent target expression of pro‐inflammatory genes by HT (Figure ). Considering that ROS activate NF‐κB, which in turn triggers the expression of inflammasome NLRP3 components, cytokines, chemokines and adhesion molecules, inhibition of NF‐κB signaling by HT, in association with its potent antioxidant capacity, supports the anti‐inflammatory effects of HT. Together, data reported indicate that DHA and HT co‐administration suppresses HFD‐induced liver pro‐inflammatory state by down‐regulation of NF‐κB signaling (Figure ), which is associated with the enhancement the antioxidant capacity of the liver over control values (Figure ) and supported by the significant inverse correlation established between NF‐κB DNA binding and that of Nrf2 ( r = −.90; p < .001).…”

“…The latter finding is associated with decreased liver FFA influx and increased FAO that may contribute to diminish hepatic TG and VLDL synthesis . Second, the protective effects of HT in liver injury models are primarily related to its polyphenolic structure, which confers its free‐radical scavenging and metal chelating properties, therefore lowering free‐radical levels and oxidative stress status (Figure ), with the concomitant increase the antioxidant potential of the liver (Figure 5). Consequently, HT may favor FAO over de novo lipogenesis through maintenance of the basal level of n‐ 3 LCPUFAs that supports PPAR‐α (Figure ) over SREBP‐1c (Figure ) functioning.…”

“…66 The antiinflammatory effect exerted by DHA is characterized by being more effective than that of arachidonic acid (C20:4n-6; AA) 65 and opposite to that of palmitic acid. 64 In addition to DHA, HT is known to exert beneficial effects related to the metabolic syndrome and its complications by diminishing oxidative stress and inflammation, as demonstrated in different biological models using several inflammation inducers, 52,53 including rats subjected to HFD for 5 weeks. 67 Data presented using mice fed a HFD for 12 weeks show significant decreases (p < .05) in NF-κB up-regulation and NF-κB-dependent target expression of pro-inflammatory genes by HT ( Figure 6).…”

“…Hepatic NF-κB DNA binding (a) and NF-κB mRNA levels (b), and tumor necrosis factor α (TNF-α) mRNA levels in liver (c) and in serum (d), interleukin 6 (IL-6) mRNA levels in liver (e) and in serum (f) and IL-1β mRNA levels in liver (g) and in serum (h). For group definition, data expression and significance design see legend to Figure 1 expression of inflammasome NLRP3 components, cytokines, chemokines and adhesion molecules, 68 inhibition of NF-κB signaling by HT, in association with its potent antioxidant capacity, 52,53 supports the anti-inflammatory effects of HT. Together, data reported indicate that DHA and HT co-administration suppresses HFD-induced liver pro-inflammatory state by down-regulation of NF-κB signaling ( Figure 6), which is associated with the enhancement the antioxidant capacity of the liver over control values ( Figure 5) and supported by the significant inverse correlation established between NF-κB DNA binding and that of Nrf2 (r = −.90; p < .001).…”

Hydroxytyrosol prevents dermal papilla cells inflammation under oxidative stress by inducing autophagy

“…HT is well established that has extensive benefits to the reduction of metabolic syndrome (Mets) and its associated complications, owing to its protective effect of health towards inflammation and OS . Among the different patterns of hair loss, AGA is most strongly connected with Mets and metabolic‐related conditions, especially in male patients .…”