Leptin and cardivascular diseases 

Researchers get more and more data on the effect of adipose tissue on the functioning of the cardiovascular system and its role in the development of CVD diseases. Lipocytes act through the biologically active substances which they produce.

Over the past thirty years, the prevalence of obesity in the world has increased by almost a third in adults and almost a half in children. It turns out that extra pounds are the most significant problem of all modern medicine. This article will tell you about the role of leptin in this question.

Contents

1. Causes of obesity.
2. The way how dysfunction of the heart and blood occurs.
3. Adipokines.
4. Summarize.

Causes of obesity

There are a lot of triggers that provoke a weight gain. However, the main one is a violation of human eating behavior.

Serious reasons include:

• genetic predisposition;
• sedentary lifestyle;
• hormonal imbalance;
• socio-economic factors;
• cultural traditions.

Most scientists are inclined to believe that obesity develops with a lack of cholesterol esterases in the human body. This enzyme (LIPA) breaks down triglycerides and cholesterol esters. They are transported by hydrolysis to lysosomes, known as intracellular organelles with hydrolytic enzymes. The lack of the enzyme provokes intracellular accumulation of triglycerides and loss of control over cholesterol synthesis. This manifests itself in the development of storage disease and Wolman syndrome, which means a deficiency of lysosomal acid lipase.

There are also genetic problems in addition to enzymatic ones. There are many genes that control obesity and overweight. For example: PPARG, FABP2, ADRB2, ADRB3. A mutation in only one of them leads to pathological changes. Low physical activity and progressive hypokinesia in all spheres of human life take the last place of top triggers.

The way how dysfunction of the heart and blood occurs

Obesity is a key factor in the formation of heart problems. The pathology of the heart and blood vessels is a consequence of disturbances in the balanced work of fat cells. It provokes a chronic inflammation in the human body. Lipoid tissue produces bioactive components known as adipokines. They take on the role of inflammatory mediators. Everything that surrounds fat cells affects the synthesis of bioactive substances, which means tissues and organs.

Obesity generally leads to an increase in the level of pro-inflammatory adipokines and a decrease in the concentration of anti-inflammatory adipokines. Thus, conditions are created for the development of obesity, and cardiovascular pathologies in the future. Products of lipocytes from different fat layers enter the bloodstream, and with the blood flow they are carried throughout the body, reaching the heart and arteries.

Here they directly influence the bioendocrine way on the tissues of the heart and the walls of blood vessels. In addition, fatty bioactive substances are able to move from one vessel to another, thus regulating the work of the entire bloodstream. This is the so-called «vasocrine» control.

Dissemination of fat cells also provokes significant changes in terms of morphology:

• excessive formation of new cells or hyperplasia;
• underlying hypertrophy or increase in the mass and volume of organs and tissues.

Ultimately, this leads to a violation of the function of the fatty layer. The growth of fat cells in volume in patients with obesity, as a rule, is due to overeating and physical inactivity. This is correlated with mitochondrial dysfunction and changes in cell wall proteins, apoptosis (death) of cells, and the development of inflammation at the biochemical level.

The pathological distribution of fat is associated with increased infiltration of active immune and connective tissue, matrix cells. Adipose tissue controls vascular tone. Normally, this occurs due to the release of vasodilator molecules such as hydrogen sulfide or adiponectin. Minimization of these mediators in obesity contributes to the development of vasomotor dysfunction.

Adipose tissue located along the perimeter of the vessels changes angiogenesis, which is directly related to an increase in blood pressure. The high activity of oxidative processes in the body becomes a source of free radicals that provoke oxidative stress and increase the risk of organ injury. It can be mediated by numerous factors. Vascular inflammation is additionally activated by the synthesis of vascular endothelial cells, which are activated by interleukins, and adipokines. Some factors provoke fibrosis of the heart.

Adipokines

Altered secretion of bioactive components of adipose tissue causes an increased risk of cardiac pathologies in obese patients. A number of new adipokines have been discovered today.

Leptin is the first of them:

1. This hormone controls body weight by regulating food and energy expenditure. This is the key to energy homeostasis, which controls the preservation of neuroendocrine potential until reproduction. Normally, leptin balances blood pressure by controlling the release of nitric oxide and angiotensin II from the endothelium. It creates sympathetic vasoconstriction. In this case, the layer of smooth muscle cells is the most important target for the hormone. This adipokine minimizes the passive tension of the vascular wall, initiates the work of the endothelium, and vasodilation. Obesity stimulates leptin resistance, so the hormone hypersynthesis can be seen as a compensatory mechanism to overcome it. In parallel, such vasodilation is considered as a signal for the protection of atherosclerosis. Obesity-induced leptin resistance can shift this delicate balance in favor of atherogenicity in healthy patients. In other words, the significance of leptin as a litmus test of cardiovascular pathologies in this case is small. It is impossible to focus in therapy only on its correction. But it should be noted that the concentration of the hormone in the bloodstream drops. Its normal functioning is restored after bariatric surgery associated with minimizing the volume of the stomach.
2. Adiponectin is an adipokine synthesized almost exclusively in adipose tissue. It circulates in three main forms in plasma: low, medium, and high molecular weight. Adiponectin improves insulin sensitivity and reduces inflammation. In clinical practice, the level of this bioactive substance has a positive effect on the course of coronary disease, prevents relapses, and minimizes mortality from cardiovascular diseases;
3. Omentin in the blood is determined in two forms: omentin-1 and omentin-2. The first form is the predominant one. Omentin-1 is mainly a product of the stroma of fat cells, so has anti-inflammatory, and antioxidant activity. The level of the biosubstance falls in obesity people in inverse proportion to BMI, waist circumference, and markers of the metabolic syndrome. Omentin-1 is also lowered in patients with coronary heart disease. Omentin-1 rises in case of a weight loss diet. Its further highlighting is associated with obesity. In addition, high plasma concentrations of omentin are correlated with improved cardiac function after reperfusion therapy in patients with AMI (acute myocardial infarction).
4. Osteopontin, like osteonectin, is a glycoprotein of matrix proteins. It is secreted by cells of the stroma, blood vessels, and directly by adipocytes. It is regulated by various pro-inflammatory mediators that increase in obesity, type 2 diabetes, and cardiovascular disease. Osteopontin works as a pro-inflammatory cytokine, the basis of cell-mediated immunity. It turns out that this is an important signaling molecule. Its mechanism of action is not completely clear. It is assumed that the bioactive substance stimulates the migration of endothelial cells, increasing the risk of atherosclerosis. It is possible that osteopontin activates macrophages. It is also secreted by Cooper cells, hepatocytes in non-alcoholic fatty liver disease and can increase the risk of cardiometabolic pathologies.
5. Visfatin is produced by fat cells, macrophages, and inflamed endothelium. Its blood levels rise in obesity, insulin resistance, and type 2 diabetes. The biological substance works as a pro-inflammatory mediator, inducing matrix enzymes in monocytes and endothelium. It is an essential link in the development of vascular inflammation in obesity and type 2 diabetes. In addition, it leads to the instability of atherosclerotic plaques. High levels of visfatin correlate with a high risk of complications after myocardial infarction. The level of visfatin in the blood decreases after bariatric surgery.
6. Ghrelin is an endogenous stimulus for the growth hormone receptor. It exists in two isovariants in the bloodstream: acylated and deacylated. These forms have opposite effects on glucose deposition from the liver. Ghrelin plays an important role in the development of cardiovascular pathology. There is a direct and indirect effect of ghrelin on the heart and blood vessels: physiological with a balance of hormonal and energy levels, regulation of the activity of peripheral nerves. Ghrelin is able to influence the functioning of the renin-angiotensin system, lowering blood pressure, and minimizing the risk of developing heart problems. It balances the level of norepinephrine in the blood, while the heart rate does not change. The myocardium is a ghrelin depot, so the substance works as a cardioprotector, increasing the contractility of the heart muscle, minimizing cardiac fibrosis, inflammation, and death of cardiomyocytes. It also protects the heart from ischemia. A hypercaloric diet can lower the level of the hormone.

Summarize

The main factor in the development of obesity is dysfunction of adipose tissue with hypertrophy of lipocytes, acute inflammation, fibrosis, and impaired vascular function. Adipose tissue is in contact with many internal organs through pro-inflammatory and anti-inflammatory bioactive substances or adipokines. Their imbalance leads to disruption of homeostasis, initiates metabolic complications from obesity. We have listed only the main adipokines. It is worth waiting for new discoveries that will help find more effective ways to correct obesity and the pathologies that it provokes.