CHAPTER I INTRODUCTION
I .1. Background of study
High-fat diet is the second most lethal habit after smoking which causes approximately 300,000 deaths a year.1,2 High fat diet often leads to excess weight gain which increase the risk of obesity, a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems. People are considered obese when their body mass index (BMI), a measurement obtained by dividing a person's weight in kilograms by the square of the person's height in metres, exceeds 30 kg/m.2,3
In obesity, the adipose tissue itself undergoes changes in cell size which alters its normal physiological function. Obesity alters adipose tissue metabolic and endocrine function and leads to an increased release of fatty acids, hormones, and proinflammatory molecules that contribute to obesity associated complications. Furthermore, an increasing number of adipokines are directly linked to inflammation and the inflammatory response and these encompass classical cytokines and one of them is interleukin 6 (IL-6).4 In addition, adiponectin, a major adipocyte-derived hormone with a role in insulin sensitivity, has a distinct antiinflammatoryaction.5 Metabolic complications of excess body fat and obesity is a significant early risk factor of cardiovascular disease and diabetes . In obesity, adipocytes produce proinflammatory cytokines,
including tumor necrosis factor and interleukin 6 (IL-6). IL-6 stimulates the hepatic synthesis of C-reactive protein.CRP), an inflammatory marker and elevated concentrations of CRP and IL-6 correlate with components of the metabolic syndrome, including elevated body mass index (BMI), high triacylglycerol concentrations, low HDL-cholesterol concentra-tions, elevated systolic blood pressure, and impaired glucose tolerance.6
Inflammation process caused by obesity has an impact on the heart health.
Heart disease or cardiovascular disease (CVD) resulted from a process called atherosclerosis which is directly linked to dietary fat.7 Fatty foods are high in cholesterol and free radicals. Free radicals are oxygen molecules that have lost an electron, and become highly reactive. As they circulate in the blood, they snatch electrons away from other molecules, sometimes grabbing them from the cells that line artery walls. The microscopic injuries that free radicals inflict begin a decades-long process that eventually narrows the arteries with cholesterol-rich deposits called plaques.8 Sometimes plaques rupture, spilling their contents into the blood. If a plaque ruptures in one of the coronary arteries that nourish the heart, its debris can cause completely blockage. Without food and oxygen to nourish its hard-working cells, part of the heart dies.
A study demonstrated that IL6 and CRP have been associated with atherosclerosis and have been shown to be predictors for coronary heart disease (CHD) development.9Consumption of virgin olive oil is effective in decreasing IL6 and CRP in stable CHD patients.10 The traditional Mediterranean diet in
the low incidence rates of myocardial infarction in Southern-Europe countries in comparison with the Northern ones.11 Olive oil is the product of transformation obtained from the olive fruit (Oleaeuropaea). The extract virgin olive oil is a very important element to make a large uptake of substances such as polyunsaturated fatty acids, vitamins and antioxidants, which play an important nutraceutical role (nutritional and pharmaceutical) in the organism.12 Monounsaturated fatty acids (MUFA) rich-diets have been associated with a low risk for coronary heart disease (CHD).13 Olive oil however is better than a MUFA-fat because it contains high amounts of antioxidant phenolic compounds (PC).14Several in vitro and in vivo studies have examined the anti-inflammatory properties of olive oil and its PC.15 It was suggested that consumption of virgin olive oil, could provide beneficial effects in stable coronary heart disease patients as an additional intervention to the pharmacological treatment. Previous study shows that association of olive oil (3mL/kg per day) for 30 days of treatments and dietary restriction is effective on the lipid profile and myocardial antioxidant defences in Rat.16 However there is no the data demonstrates olive oil effects on the inflammatory markers in atherosclerosis Rat. Further in vivo study of olive oil efficacy related to the inflammation process by using Rat as experimental animal is merit to be contemplated. Therefore, this current study is aimed to the effects of olive oil on high fat diet (three kind of difference doses level 1, 2, and 3 mL/kg/dayfor 30 days of treatments period) on the IL-6 and CRP as inflammatory markers in Rat undergo atherosclerosis.
I .2. Research Questions
I .2.1. The major research question in this study:
Does extra olive oil have an effect toward inflammation in high fat diet induced atherosclerosis of wistar rats ?
I .2.2. The minor research question in this study:
a. Does extra olive oil (1, 2, and 3 mL/kg/day) reduce the level of IL-6 in high fat diet wistarrats ?
b. Does extra olive oil ( 1, 2, and 3 mL/kg/day) reduce the level of CRP in high fat diet wistar rats ?
I .3.Research Objective:
I .3.1. General Objective
To investigate the extra virgin olive oil have an effect to IL6 and CRP in high fat diet wistar rats.
I .3.2. Specific Objective
a. To proof the of olive oil 1, 2, and 3 mL/kg/day in reducing the level of IL-6 in high fat diet wistar rats.
b. To proof the of olive oil 1, 2, and 3 mL/kg/day in reducing the level of CRP in high fat diet wistar rats.
I .4. Research Benefits:
Through this study on the role of olive oil to protect inflammation in high
as an alternative solution toward such problem related to human health disorder.
In this case, when modern drugs are disappointing because of the availability of their side effects, utilizing olive oil as natural products in the diet type may open up our mind to find a preventive agent of high fat diet . By thorough evaluation of the potency and optimal dose of olive oil as therapy of high fat diet, we are looking forward an ideal medication that is not merely for the most potent in efficacy but also to the fulfillment of the bio-safety requirement.
I .5. Reserach Originality
There were many reports about olive oil application to solve the disease problem related with high fat diet and hypercholesterolemia lead the atherosclerosis case, however the data demonstrate its effect on the IL-6 and CRP as pro-inflammatory process is still unclear in recent time. This investigation is addressed to delineate the role of olive oil as anti-inflammation agent refers to the involvement of IL-6 and CRP in the inflammation process lead to development of atherosclerosis in vivo for the first time by using rats as an experimental animal.
Table1. Previous report related to study on protective effect olive oil on high fat diet.
No Title publication
and authors Method Results
1. Review,Olive oil in the primary prevention of cardiovascular disease Canela MR, Gonzale MAM. 2010.17
Epidemiological studies Countries that contain olive oil cultivation areas less injury by acute myocardial infarction 2. Effect of Vildagliptin on
Atherosclerosis Progression in HighCholesterol –Fed Male Rabbits .Hadi NR, Abdulkadhim H, Almudhafer A, Majeed SA.2013.18
6 rabbits for each group: Group I rabbits fed normal chow (oxiod) . Group II rabbits fed 1% cholesterol enriched diet for 24 weeks. Group III rabbits fed with cholesterol enriched diet for 6 weeks, and treated with vildaglipin 50 mg/kg/day orally for thenext 6 weeks. Blood samples werecollected at the start of the study, at 6weeks of the study and then at the end of treatment course to measure Serum lipids profile [(TC), (TG), (HDL)], hsCRP and TNFα. At the end of the study theaorta were removed for measurement of aortic MDA, glutathione, sectioning forhistopathology and
measuring aortic intima- media thickness
Treatment of rabbits with vildagliptin for 6 weeks lead to a significant reduction in serum level of TC, TG, hsCRP and TNFα and a significant increase in serum HDL level.
3. The effect of olive oil polyphenols on antibodies against oxidized LDL.
A randomized clinical trial .Olga Castañer , Montserrat Fitó, M.
Carmen López- Sabater.2011.19
In a crossover, controlled trial, 200 healthy men were randomly assigned to 3-week sequencesof 25 mL/day of 3 olive oilswith high (366 mg/kg), medium (164 mg/kg), and low (2.7 mg/kg) phenolic
content.
Plasma autoantibodies against oxLDL( OLAB )concentration was inversely associated with oxLDL (p < 0.001).
Olive oil phenolic content increased OLAB generation, with the effect being stronger at higher concentrations of oxLDL (p ¼ 0.020 for interaction). A direct relationship was
observed between OLAB and the total olive oil phenol content in LDL (r
No Title publication
and authors Method Results
increased directly in a dose-dependent manner with the polyphenol content of the olive oil administered (p ¼ 0.023).
4. The long-term ingestion of a diet high in extra virgin olive oil produces obesity and insulin resistance but protects endothelial function in rats: a preliminary study.Hady Keita , Eduardo Ramírez-San Juan , Norma Paniagua- Castro, Leticia Garduño- Siciliano and Lucía Quevedo.2013.20
Wistar rats divided to 27 rats each group 9 rats group I.
commercial diet and AND GROUP II EVOO 25% and group III margarine diet for 20 weeks.
EVOO and M weight were significantly higher in both of (EVOO and M) and at week 20 inject by glucose it showed increase glycemia after 15 minutes and it decreased after 30 minutes and M group showed high LDL than EVOO and control
5. Effect of Mediterranean diet on the expression of pro-atherogenic genes in a population at high cardiovascular risk.
Cortés VL, Estruch R, Mena MP, Ros
E, González MAM, Fitó M, Raventós
RML,Badimon L.2009.21
Participwere 49 (23 men, 26 women), aged 55–80 years. It divided to 3 groups, group I TMD+VOO and group II TMD+NUTS and group III C+
onocytes were isolated from blood before and 3 months after dietary intervention. We analyzed the expression of genes involved in inflammation [cyclooxygenase-1 (COX- 1),cyclooxygenase-2 (COX-2) and monocyte chemoattractant protein (MCP-1)], genes involved in foam cell formation [low-density lipoprotein receptor-related protein (LRP1), LDL receptor and CD36], and genes involved in thrombosis [tissue factor (TF) and tissue factor pathway inhibitor (TFPI).
TMD + VOO
intervention prevented an increase in COX-2 and LRP1, and reduced MCP-1 expression compared to TMD + nuts or control diet
interventions.
TMD + nuts specifically increased the expression of CD36 and TFPI compared to
TMD + VOO and control diet intervention.Our findings showed that the Mediterranean diet influences expression of key genes involved in vascular inflammation, foam cell formation and thrombosis. Dietary intervention can thus activelymodulate the expression of pro- atherothrombotic genes even in a high-risk population.
