Obesity is a strong risk factor for developing dyslipidemia [30, 31], diabetes mellitus , fatty liver (which can later progress to nonalcoholic fatty liver disease , cardiovascular (CV) diseases such as heart failure (HF) and coronary heart disease (CHD) .
Feeding of (HFD) to rats was proved to be a useful model of putative effects of dietary fat in humans . Rat models are therefore useful tools for inducing obesity as they will readily gain weight when fed high-fat diets .
In the present study, obesity was induced in white albino rats by using a high fat diet formula. Obesity was induced in 16 weeks. The weight gained by rats fed HFD formula, was significantly more than that gained by those fed the normal diet. Many workers were able to induce obesity in rats using different formulas of high fat diets [16, 35–38]. The response of animals to the HFD is a subtle but cumulative effect, because it took over a 10 weeks period. The difference in weight gain in all above studies may be due to age, genetic makeup of the different strains and composition of different formulas [35, 36].
HDF resulted in dyslipidemic changes as illustrated by increasing serum levels of triacylglyceral, total cholesterol, LDL-cholesterol and VLDL-cholesterol and low level of HDL cholesterol as compared with control; a finding in accordance with that of Woo et al , and Kamal and mohamed . Dyslipidemic changes occurs in obesity may be due to the increased triacylglycerol, content of the liver due to increased influx of excess NEFAs into the liver. It has been revealed that altered lipid concentrations and qualitative changes of the lipoprotein fractions in obesity are associated with an increased risk of various adverse effects of obesity [42, 43]. Additionally, lipid alterations have been considered as contributory factors to oxidative stress in obesity . Increased production of reactive oxygen species as well as reduced antioxidant defense mechanisms have been suggested to play a role in both humans and animal models of obesity [3, 45].
Lipid peroxidation is thought to be a component of obesity-induced pathology . The data presented in this study showed that obesity increased lipid peroxidation in hepatic, cardiac and renal tissues as expressed by increased tissue levels of MDA.
Our results are in basic agreement with the results of Vincent, et al., , Olusi et al., , and Amirkhizi et al.,  who showed that, obesity is an independent risk factor for increasing lipid peroxidation and decreased activity of cytoprotective enzymes. Obesity can cause increased lipid peroxidation by progressive and cumulative cell injury resulting from pressure of the large body mass. Cell injury causes the release of cytokines, especially tumor necrosis factor alpha (TNF-α) which generates ROS from the tissues which in turn cause lipid peroxidation . The hypertriglyceridemia seen in obese rats may contribute to the alteration in the oxidant-antioxidant balance, suggesting that an increase in the bioavailability of free fatty acids can increase lipid peroxidation .
Cellular proteins are believed to be the target of free radical-induced oxidative injury. Protein carbonyl (PCO) content of liver, heart and kidney is increased significantly in obese rats compared to normal rats. Increasing PCO in obesity may be due to damage of cellular proteins by ROS generated in obesity. The accumulation of oxidized proteins might impair the cell function. The use of PCO as a marker for measuring of damaged proteins may have some advantages over other markers, because of relatively early formation, greater stability and reliability and also their longer life-span .
There are several potential mechanisms for of the increasing lipid peroxidation and protein carbonyl in hepatic, cardiac and renal tissues. Reactive oxygen species (ROS) and lipid peroxidation products impaired the respiratory chain in hepatocytes either directly or indirectly through oxidative damage to the mitochondrial genome. These features, in turn, lead to the generation of more ROS, and a vicious cycle ensues. Mitochondrial dysfunction can also lead to apoptosis or necrosis depending on the energy status of the cell. Finally, ROS and lipid peroxidation products also activate stellate cells, thus resulting in fibrosis [50, 51].
Lipid peroxidation in the heart leads to loss of the cellular membrane integrity due to oxidative modification of lipids and proteins that can ultimately lead to cardiac arrhythmias, poor contractility, infarction, cardiac failure or sudden death . The potential mechanism for increased lipid peroxidation in cardiac tissue may be due increased lipid substrate within the myocardium in which can serve as a larger target for oxidation by free radicals [47, 52]. It is well established that elevated myocardial work and mechanical overload is associated with increased free radical production consequently lipid peroxidation . Mechanical overload-induced increases in muscle oxygen consumption accelerate electron flux through the mitochondria in proportion to the need for ATP. This results in increased electron leakage from the electron transport chain and increased production of superoxide anions .
Several mechanisms may contribute to the onset and/or the progression of renal involvement in experimental obesity among them; lipid peroxidation and oxidative stress have been frequently proposed. HFD induces alteration of renal lipid metabolism by an imbalance between lipogenesis and lipolysis in the kidney, as well as systemic metabolic abnormalities and subsequent renal lipid accumulation and lipid peroxidation leading to renal injury . The accumulation of adipose tissue around the kidneys of obese rats penetrates into the medullary sinuses thus increased intrarenal pressures which may cause damage the renal tissue. Damaged renal tissue acts as sources of ROS and develops lipid peroxidation. An increased lipid peroxidation in the kidney tissue, as well as modification of the circulating LDL/VLDL fraction, is probably involved in the onset of kidney lesions in this normoglycaemic rodent model of obesity .
It has been shown that animal body had an effective mechanism to prevent the free radical induced tissue cell damage, this accomplished by a set of endogenous antioxidant enzymes and protein such as GST, SOD, CAT, GPX, GRD and GSH. When the balance between ROS production and antioxidant defense is lost oxidative stress results; which through a serious of events deregulates the cellular functions leading various pathological conditions . GST, CAT and GPX constituted a mutually supportive team of defense against reactive oxygen species. In the present study GST, CAT, GPX and PON 1 enzymes activity and GSH protein were measured in hepatic, cardiac and renal tissue and the data showed clearly a significant decrease in the activities of GST, GPx and PON 1 enzymes in liver, heart and renal tissues in obese rats as compared to the control group. Catalase (CAT) enzyme showed a non significant change in hepatic and heart tissues and decreased in renal tissues of obese rats. GSH level showed significant decrease in both liver and renal tissues in obese rats. While its level in heart tissues showed significant increase in obese rats. Our results were in agreement with many authors [[8, 47, 50] and ]. There are several mechanisms explaining the reduction of antioxidant enzymes in obese rats;
The increased lipid peroxidation lead to inactivation of the enzymes by crosses linking with MDA; this will cause an increased accumulation of superoxide, H2O2 and hydroxyl radicals which could further stimulate lipid peroxidation. This mechanism has a clue from work of Demori et al., (2006)  and Moyà et al., 2008  who showed that the liver catalase, glutathione peroxidase, and Mn-superoxide dismutase were reduced in response to the cafeteria-diet feeding in obese rats. Furthermore our correlation study indicated that there is negative correlation between MDA and PCO levels and enzymes activities of GPx, GST and PON 1 in the liver, heart and renal tissues and with CAT enzyme activity in kidney. This correlation finding conformed and supported the concept of inactivation of antioxidant enzymes and proteins by high level of lipid peroxidation in obesity.
Decrease of antioxidant enzyme may be due to rapid consumption and exhaustion of storage of this enzyme in fighting free radicals generated during development of obesity.
PON-1 activity could be decreased as consequence of an altered synthesis and/or secretion of HDL secondary to impaired lecithin cholesterol acyl transferase (LCAT) activity.
Under oxidative stress, PON-1 may be inactivated by Sglutathionylation a redox regulatory mechanism characterized by the formation of mixed disulfide between a protein thiol and oxidized glutathione .
In the present study, the non significant change in the CAT enzyme activity in liver and heart tissues of obese rat may be due to increases oxygen consumption of previous tissues due to obesity and the change of CAT enzyme activity is dependent on oxygen consumption [12, 47]. As stated above, cardiac tissue of obese rats showed significant high content of GSH compared to normal rats. Vincent1, et al., demonstrated similar results. Increasing of GSH concentration in cardiac tissue in obese rats in response to free radical formation in an effort to protect cells against oxidative damage . The adaptation of the primary antioxidant defense in the hearts of high-fat-fed animals appeared to be less complete, as indicated by the failure of other antioxidant enzyme activities including GST, GPX and PON 1 to increase in the hearts of animals on the high-fat diet. Non significant correlation was detected between MDA or PCO levels and CAT enzyme activity in the liver and heart tissues.