11. Obesity: introduction

1.

Obesity is a modern endemic. This is a well-known fact, but little is known about the root of the problem, namely that younger and younger children are affected by this disease every year.

Similarly, it is known that obesity can cause several diseases from diabetes to hypertension, but it is extremely important to understand that obesity is a disease in itself. As any other disease, it can be classified, and needs medical treatment.

Obesity is also a disease of a distorted of perception of the body or body-scheme. It is the opposite of anorexia, when the patient feels herself obese with normal body parameters and as a result a pathologic fasting is destroys normal physiological processes in a multi-organic fashion. The patient has a distorted perception of his/her own body scheme.

Obesity is a disease that affects large populations. Hungary is strongly affected by this problem. For a deeper understanding of the underlying mechanisms of obesity, let us see what the body is made of.

On tissue-level, in the body of a healthy middle aged man the most abundant tissue is the muscle and right after that comes the adipose tissue. If we investigate on cell compartment level, after water, the largest pool of molecules is not that of the proteins and enzymes, but the lipids.

Obesity is controlled by quite simple mechanisms. For this we have to understand the regulation of appetite, which is performed in the nucleus arcuatus, involving two types of neurons: orexigenic and anorexigenic ones.

In the course of a year, a person consumes hundreds, or even thousands of kilograms of food. If there is a slight deregulation in the controlling appetite and body weight, this can have severe consequences. Imagine a 20-kilogram increase or decrease in weight per year for a person who is not overweight. This might be a sign of a serious disease and could have severe consequences.

Orexigenic and anorexigenic neurons together regulate the appetite: by comparing our self-perception to our actual body, our appetite is increased or decreased accordingly. The inputs of this system are important and we can differentiate basically among four types of input. Leptin, released by the adipose tissue is a signaling molecule that translates the total level of adipose tissue to the neurons. Leptin provides the input to a so called adipostat. The adipostat regulates the total level of adipose tissue available in the body. In obesity the adipostat is set to a higher value and the patient will do everything to maintain its adipose tissue levels intact. The mechanism works in a similar way to a thermostat. If it is set to a higher temperature, you will overheat your apartment and thereby consume a lot of energy. The energy waste increases in proportion to the increase of the external temperature.

Another protein involved in the regulation of the appetite is insulin. Insulin is decreasing body temperature. If we eat and the blood sugar level increases, our appetite will decrease.

Another two important signaling molecules are Ghrelin, released from the stomach, and PYY, released from the colon.

As a general principle, we can state that weight gain and weight loss follows the laws of termodynamics. Energy input has to equal the consumption to be in a steady state level, thus,any change can produce weight gain or weight loss.

Figure 11.1. Figure 11.1. Obesity: environmental cultural and internal factors regulate

energy input. Energy inpit and consuption has to be in balance

11. Obesity: introduction

Obesity: environmental and social effects. Balance of energy input and output Weight increase obeys the laws of thermodynamics. The balance of energy intake and energy output produces increase or decrease in weight. The energy output consists of 3 components:

1. basic metabolism;

2. TEF: thermic effect of food;

3. energy consumed by physical exercise.

Energy consumption consits of several components. Basal metabolism plus TEF (thermic effect of food) and physical activity together represent the total energy consumption. The energy provided by food is delivered in the form of three different types of molecules: sugars, lipids and proteins. Other factors also influence the energy balance. Energy consumption is proportional to the total amount of lipids. Lower sympathetic activity favors weight gain, while beta agonists can increase heat production through the UCP proteins. The transcription factor PPAR gamma is responsible for terminal differentiation of adipocytes and lipid accumulation.

The energy is supplied to the organism in the form of 3 type of molecules: proteins, carbohydrates and lipids.

The energy balance is related to other factors as well. 1. The energy consumption is directly proportional to the amount of available triglicerids. 2. Lower sympathetic activity is causing weight increase. 3. Betaagonists increase the release of heat through UCP proteins. 4. The transcription factor PPAR gamma facilitates the terminal differentiation of adipocytes.

Twin studies have shown that from all cases of obesity, 60% is not genetically inherited, 30% has a genetic component and 10% is culturally determined. The genetically determined cases are usually more severe. From the perspective of molecular medicine, these cases are most relevant.

Twin studies

It has become evident from twin studies that 60% of overweight cases are not genetically inherited. 30% are genetically inherited, while 10% show cultural transmission. In the genetically determined overweight cases, the prevalence of extreme obesity is more frequent. The non-genetically determined overweight cases are more commonly associated with increased appetite because of indirect effects. From the point of view of molecular medicine, the cases with genetic transmission are of special interest (stress and psychological disorders).

Figure 11.2. Figure 11. 2 Twin studies and the genetics of obesity

11. Obesity: introduction