Hydroxytyrosol better than oleuropein in a high fat diet feed rats study

A very recent study (“Comparative study on beneficial effects of hydroxytyrosol (HT) and oleuropein (OL)-rich olive leaf extracts on high fat diet induced lipid metabolism disturbance and liver injury in rats”; Biomed Res. Int.; Ines Fki et al; 2020) concluded that oleuropein and hydroxytyrosol exerts protective effects on high fat diet (HFD) induced against body weight gain by preventing the white adipose tissue overgrowth. In addition to this, the enhanced extracts were capable of protection against the lipid metabolism perturbation and the degenerative changes in the hepatic cells induced by the HFD, not only by enhancing the antioxidant system activity in the cells but also by blocking the expression of the proteins involved in the inflammation and liver damage.

Hydroxytyrosol performed better than oleuropein in most of the tested markers.

Weight gain:

The HFD increased the body weight and adipose tissue mass in control and treatment (25% and 50%). OL and HT reduced the body weight by 63% both of them. Both decreased the epipidymal adipose tissue weight when compared with the HFD.

HT and OL displayed a significant reduction in the adipocyte size. This could be mediated by the adipogenesis.

Lipid parameters:

In HFD rats there was a significant increase in cholesterol (53%), tryglicerides (169%) and LDL-cholesterol (146%) as compared to control.

Control HFD OL HT
Total chol 1,07 1,64 1,22 1,16
HDL 0,5 0,22 0,34 0,45*
LDL 0,39 0,96 0,72 0,44*
Tryglicerides 0,83 2,24 1,28 1,21

 

 

 

 

 

It is perceived how the HT supplementation ever recovered and evn improved the control HDL levels.

Blood glucose, insulin and HOMA-IR levels:

Control HFD OL HT
Glucose (g/l) 7 9,5 8,5 7,2*
Insulin (mg(ml) 0,5 1,75 0,8 0,65*
HOMA IR index 5 22 9,5 6,5*

 

 

 

 

HT also showed a brilliant result in the glucose levels as compared with OL.

 Plasma levels of liver injury biomarkers:

Control HFD OL HT
Liver weight 35,74 43,09 35,19 35,53
AST 76 165,66 100,5 98,66
ALT 28 61 37,33 26,5*
LDH 202,75 647,87 333,5 270,5

 

 

 

 

 

ALT levels were also similar to the control group.

 Liver oxidative stress parameters:

Control HFD OL HT
MDA (nmol/g tissue) 2 3,75 2,75 2,3*
Trolox (µM) 47.000 20.500 33.000 44.000*
CAT (U/mg protein) 32 15 22 27
SOD (U/mg protein) 137 37,5 80 110

 

 

 

 

Plasma levels of leptin and TNF-alpha:

Control HFD OL HT
Leptin (ng/ml) 1,75 3,25 1,9 1,65*
TNF-alpha (pg/ml) 1 0 0 1

 

This reduction of leptin led to a reduction of proinflammatory response and prevention of excessive celular stress by diminishing TNF-alpha. HT offered greater improvement of leptin and TNF-alpha levels.

The histopathological analysis of the HFD-fed rats hepatic tissue showed a steatosis and inflammatory damage. There was inflammatory cell infiltration and a steatosis by the lipid droplet accumulation in the cytoplasm of the hepatocytes.

OL and HT decreased the lipid accumulation and inflammation in liver tissue. Both also decreased COX-2 and TNF-alpha considerably.

All these findings are terribly valuable for Non Alcoholic Fatty Liver Disease (NAFLD).

NAFLD consists of a fat accumulation and inflammation. The increase of TG is in response to the augmented influx of the fatty acids from the adipose tissue to the liver and the improved endogenous fatty acid synthesis. HT supplementation is more beneficial for the recovery of the liver function than OL treatment.

The oxidative stress also plays a pivotal role in NAFLD. Mitochondria continously exposed to the high levels of ROS (reactive oxygen species) can suffer from structural and functional alterations. They may contribute to the reduction of the beta-oxidation and lead to a greater accumulation of free fatty acids. OL and HT diminished MDA levels. HT offers a greater improvement of the hepàtic antioxidant status in the HFD rats.

Inflammation is known as an important mediator in the progress from NAFLD to NASH. Previous data confirmed a significant correlation between HDF and inflammation markers as TNF-alpha.

In this study HFD increased the expression of COX-2 and TNF-alpha significantly.

OL and HT repressed the liver function inflammation and down-regulated the expression of the COX-2 and TNF-alpha.

In conclusion, OL and HT displayed a positive reversion of many parameters  although HT showed a stronger activity than OL.

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