There is no single cause to explain all the cases of obesity worldwide. Environmental factors associated with obesity include socioeconomic status, ethnicity, region of residence, season, and urban living (14). Nevertheless, obesity ultimately results from an imbalance between energy intake and energy expenditure (15). Genetic predisposition may be a determinant for weight gain; however, previous findings have shown that genetic predisposition does not automatically lead to the development of obesity, because eating habits and patterns of physical activity may play a more significant role in the amount of weight gained (16,17). In addition, a sedentary lifestyle as well as psychological factors such as depression, low esteem, or absence of night sleep can also largely contribute to weight gain (18). However, although the exact cause of weight gain remains to be clarified and likely arises from a complex combination of factors such as genetic factors that greatly affect the manner in which the body regulates the appetite, and the rate at which it turns food into energy, known as the metabolic rate (19,20), excessive weight is clearly gained by consuming an excess of calories as compared to those utilized by the body, with the excess of calories being stored as fat tissue (15).

Accordingly, the quantity of fat in a person's diet may have greater impact on weight than the number of calories it contains. The majority of fat calories are immediately stored in fat cells, which add to the body's weight and girth as they expand and multiply (21) while carbohydrates such as cereals, breads, fruits, and vegetable and proteins are converted to fuel almost immediately following consumption (22). In addition, fat regimens result in excessive and abnormally higher levels of cholesterol in the blood (hypercholesterolemia) (23). Depending on the balance between the fractions of saturated and unsaturated fatty acids, fat contained in the blood circulation can immediately affect certain organs such as liver and kidney, concomitantly with devastating local actions inside of the vessels through the formation of atherosclerosis (24), an infringement of medium and large arteries due to a buildup of fat inside of the arterial wall, termed visceral fat. The latter is mainly involved in metabolic syndrome (25).

Diets that are extremely rich in carbohydrates and high doses of alcohol promote the increase of another lipid component present in the blood, that of triglycerides, which constitures an additional risk factor of the formation of atherosclerosis (24). Other factors favoring the formation of atherosclerosis include physical inactivity, smoking, stress, inflammation and certain bacteria (26). However, the fat continually accumulated in branch vessels, thus blocking the blood flow of large arteries. In agreement with these data, increased carotid intima-media thickness in obese subjects independently of blood pressure levels, even in a normotensive blood pressure range has been observed (27). This observation suggests an early course of the atherosclerotic process in obesity. Accumulation gradually increases to form a type of plaque that may continue to grow until it reaches a narrowing or stenosis of the vascular wall (28) that can continue to increase until important obstructions of arterial lumen are induced and downstream local disorders that affect organs are generated, leading to morbidity (29,30) and even sudden death (31). Another detrimental effect of high caloric intake is the increase of norepinephrine turnover in peripheral tissues, raising the resting plasma norepinephrine concentration, which is an indirect measurement of SNS activity, and amplifying the increase of plasma norepinephrine in response to stimuli such as upright posture (32). Thus, high dietary content in fat and carbohydrate has been suggested to acutely stimulate peripheral α1 and β-adrenergic receptors thereby leading to the elevation of sympathetic activity and hypertension (33). Similarly, upregulated hypothalamic tyrosine hydroxylase and hypothalamic adrenoceptor gene expression of the α2B receptor have been identified, in obese hypertensive rat (34). In addition, the pharmacological blockade of adrenergic activity in experimental models markedly decreased the rise of blood pressure in dogs fed a high-fat diet (10). Similarly, in human, combined α and β adrenergic blockade significantly reduced blood pressure in obese relative to lean patients with essential hypertension (35), although elevated heart rate seems to be the effect of decreased parasympathetic activity (36).

Overweight is a condition that affects the body composition thereby damaging and modifying the aspects of organs. Major organs feeling the brunt of obesity, include heart (37), liver (38), kidney (39), lungs (40), colon (41), skin (42), vessels (43) and brain (44). Whereas the effect on each organ is associated with collateral defects that may have serious concerns regarding health, renal injury seems, however, to be the most directly dependent on body weight, as dietary fat restriction ameliorates significantly the renal histology (45). The structural changes inside of the kidney, secondary to obesity, are important as the fat deposit around the kidneys, together with increased abdominal pressure secondary to central obesity, have been suggested as an additional cause of renal sodium reabsorption disorder. Specifically, initially, obesity causes renal vasodilatation and glomerular hyperfiltration, which act as a compensatory mechanism to maintain sodium balance despite the increased tubular reabsorption that, along with increased arterial blood pressure and metabolic abnormalities as well as other factors such as inflammation, oxidative stress, and lipotoxicity, may contribute to the exacerbation of renal injury or dysfunction through a vicious cycle (46,47). These factors result in clinical evidence of the presence of proteinuria that usually precedes the glomerular filtration rate decline over several years (48,49). The involvement of insulin and angiotensin II in the development of glomerular hyperfiltration have been shown in obese animals (42) in which, leptin, a hormone produced in adipose tissue, contributes to the development of renal injury through the induction of cytokines (50). Consistently, adipose tissues, particularly those of abdominal fat may specifically exert systemic effects through the secretion of a variety of hormones and cytokines, leading to obese-associated glomerulopathy (51).

In accordance to the abovementioned data, regimens rich in fat and carbohydrate, lead to hypercholesterolemia and free-fatty acids in the blood (23) which together with free-fatty acids released from phospholipids can act directly on ion channels of cellular membranes of smooth muscle cells and other tissues (52). They can also act as potent activators of the phosphorylation of calcium-independent isoenzyme of protein kinase C (53), a vital element in mediating signal transduction and cell regulation. The binding of free-fatty acid to NA/K-ATPase is involved in the changes of interactions between the enzyme and neighboring membrane protein to induce the formation of multiple signaling modules that results in the activation and production of the epidermal growth factor receptor that increased reactive oxygen species (54). The reduction of endothelial function is mainly the result of a decrease in nitric oxide (NO) related to an increase in oxidative stress or the result from pro-inflammatory cytokines (55). Altogether, cytokines and oxidative stress as well as the decrease of NO result in vasoconstriction and vascular resistance that are detrimental and predisposed to venous insufficiency, venous thrombosis and pulmonary embolus, cardiovascular disease and particularly to hypertension (37).

Biochemical, physiological and functional studies have suggested that the renin-angiotensin system is mainly involved in the development of hypertension through two systems including tissue and circulating (55). In agreement with this finding, adipose tissue-derived angiotensinogen, the major site in which all components of the RAS are formed, can enter the circulation. The tissue RAS was in a state of constant interaction with the blood. Angiotensinogen, angiotensin (Ang) I and AngII are locally produced and at are simultaneously taken up by the cells, in which AngII receptors are overexpressed. Angiotensinogen production serves as a cause and effect of adipocyte hypertrophy and leads to elevation of blood pressure through the action of AngII, which induces systematic vasoconstriction, direct sodium and water retention and increased aldosterone production (56). Consequently, AngII determines a high salt-sensitive blood pressure condition in obesity as it is produced at high rates and is not suppressed by volume expansion. An alternative mechanism of RAS activation may be a chronic elevation of sympathetic tone, causing renal vasoconstriction and renin-dependent chronic hypertension. The arterial blood pressure controlling mechanism of diuresis and natriuresis according to the principle of infinite feedback gain seems to be raised near the higher blood pressure value in obese patients. Abnormalities in these mechanisms tend to raise blood pressure, increase sodium and water excretion through pressure natriuresis and diuresis (57), which lead to extracellular fluid volume expansion, resulting in a hypertensive adjustment of the pressure natriuresis (10,11), a resetting of the kidney fluid apparatus to a hypertensive level, consistent with the model of hypertension because of volume overload. Another significant cause of the shift of pressure natriuresis towards higher blood pressure levels in obesity is the possibility of alterations in intrarenal forces caused by histological changes in the renal medulla that may compress the loops of Henle and vasa recta (58).

Furthermore, high levels of plasma renin activity, plasma AngII and aldosterone values were observed in human obesity (59) in which a presynaptic potentiating effect was observed on the sympathetic neurotransmission in patients under sodium restriction (60), likely through hypothetical mechanisms including impaired function of baroreceptors sensitivity and increased levels of circulating free-fatty acids, AngII, insulin and leptin (61).

Elevated levels and abnormally distributed free-fatty acids were reported in obese hypertensive in which they enhanced vascular α-adrenergic sensitivity and consequently the increase of α-adrenergic tone (62). Although the mechanisms were endogenous, the effect exerted by free-fatty remains to be investigated. At present, it has been documented that free-fatty acids inhibit Na+, K+ ATPase and the sodium pump raising vascular smooth muscle tone and resistance (54).