INTERNATIONAL UNIVERSITY OF SARAJEVOFACULTY OF ENGINEERING AND NATURAL SCIENCESDEPARTMENT OF GENETICS AND BIOENGINEERING

BIOCHEMISTRY- BIO 305

SEMINAR WORK

MECHANISMS OF BODY WEIGHT CONTROL

Students:Fatima Alihodi( 992 418)SeidMalanovi (1210197 )DelilaBjeli (992324 )Assoc.Prof.Dr. Sabina Semiz

Sarajevo, 2015Contents1.Introduction42.Carbohydrate metabolism73.Lipid metabolism114.Hormones involved in mechanism of body weight control155.Complex metabolic disorders196.Therapeutic targets of mechanism of body weight control227.Discussion and Conclusion248.References:25

AbstractBody weight is highly important for normal functioning of organism. All substances that we take in daily food intake are processed through different metabolic pathways. One of the very important classes of macronutrients are lipids and carbohydrates. Lipids are processed on a way to give the highest amount energy to the cells together with carbohydrate molecules. Level of lipids and carbs can be elevated or decreased depending on food intake and metabolic reactions in our body. By increasing lipids or carbs, we are increasing adipose tissue and that is actually bodys weight. Control of mechanisms of body weight also should be understood very well. Throughout our project we will mention lipids metabolism and carbohydrate metabolism, what affect increasing and decreasing amount of body weight as well as disorders which are more and more present in the world. By understanding the mechanisms we are able to control our weight and prevent common diseases such as obesity, diabetes, cardiovascular diseases, etc. We believe that this project can be very helpful and further studied.

Keywords: lipid metabolism, carbohydrate metabolism, weight, hormones, disorders, fat, adipose tissue, HDL, LDL, obesity, diabetes.

1. IntroductionMetabolism represents the sum of the all reactions that takes place in a living cell. They are all enzyme-catalysed reactions which allow organism to develop normally, to grow, reproduct, and to maintain structure and respond to the environment. All the reactions that take place are divided on two parts: catabolic and anabolic. In catabolic reactions, organic matter is broken down and energy is gained through cellular respiration, while in anabolic reactions energy is used in order to synthesise components such as proteins and nucleic acids. One of the connections between catabolism (catabolic reactions) and anabolism (anabolic reactions) is ATP which is used to shuttle chemical energy from catabolism to anabolism. Major biochemicals that take part in metabolism are: amino acids and proteins, nucleotides, lipids, carbohydrates, coenzymes, cofactors and minerals. All of those molecules and substances that enter the body have their own pathways of degradation and represents mechanism of body weight control and regulation of storage and usage in order to keep body weight at proper level as much as possible. Most important are lipid metabolism and glucose related pathways.Lipid metabolism represents processes related to interaction and degradation of lipids which are the most diverse group of biomolecules. They are part of cell membranes and very important as energy source. Thus, synthesis of lipids is one of the key processes for sustaining work of all mechanisms of weight control. Most lipid biosynthesis in eukaryotic cells occurs in the endoplasmic reticulum. Fatty acids are the building blocks of most lipids. Synthesis of those occurs mainly in cytoplasm of liver and adipocytes, and also in mammary glands during lactation, and all occurs in different pathway than degradation. Fatty acids are important sources of energy because, when are metabolized, they yield large amount of ATP. Also, another way for body to gain energy is by process of glycolysis. When amount of glucose is high, large amounts of Acetyl-CoA will be produced by glycolysis which can be used for fatty acid synthesis since glucose represents major fuel for tissues such as brain, muscles, etc. Process of degradation of glucose to gain energy, glycolysis, is based on conversion of glucose to pyruvate with release of free energy to form ATP and NADH. All of those molecules are essential for body to perform work and regulate storage and usage of energy and on that way regulate body weight. Both pathways of degradation and storage of lipids and glucose have in common Acetyl-CoA which is central molecule in metabolism pathways in both directions- degradation and synthesis of molecules in process of gaining energy,it's storage and usage. After food intake, it is degraded by enzymes into triglycerides, carbohydrates and proteins. All of them can be further degraded to get ATP molecule. Our body uses different enzymes and pathways because different molecules enters the process, so triglycerides are degraded to fatty acids + glycerol which further enter the process of fatty acid oxidation to make Acetyl-CoA. Carbohydrates are also degraded to monosaccharides which in process of glycolysis are decomposed to pyruvate which in further path of degradation becomes again, Acetyl-CoA.Third group of molecules, proteins, by degradation became amino acids which in process of amino acid catabolism can be decomposed into same molecule as previous two- Acetyl-CoA. Acetyl-CoA further reacts with oxaloacetate in order to produce citrate. Citrate allosterically activates enzyme Acetyl-CoA Carboxylase. It means, when there is high level of citrate in cell, it will automatically make active conversion of Acetyl-CoA to malonyl-CoA which will be further processed in production of fatty acids for storage. All those processes are regulated by synthesis and degradation of molecules, and are triggered by hormones, but also influenced by genetics and environmental factors. When there is high intake of food which is degraded and energy is produced, but body does not use it, it has to be saved in process of storage. Glucose will be stored as glycogen mostly in liver, while lipids will be stored in adipose tissue as fat. It is said that one pound of fat contains more energy than one pound of dynamite. Way how body weight is determined is according to energy intake and energy expenditure by processes we mentioned previously. Imbalance between those two causes change in body weight. Organisms use energy to perform work and efficiency of metabolism refers to the amount of energy an organism has to use in order to do a work. Of course, efficiency of metabolism is various among species and individuals among species. High metabolic efficiency means that individual needs less energy to perform some work than individual with low metabolic efficiency. Also, those individuals are able to preserve body weight in negative daily energy balance, but also more likely to gain weight during positive energy balance (expenditure exceeding intake and intake exceeding expenditure). (1)Storage of energy in form of lipids is in adipose tissue which is recognized also as major endocrine organ. It produces hormones such as leptin, estrogen, resistin and cytokine TNF. Energy stored in this tissue can be used in reversible processes when there is no enough food intake that can be degraded to energy required, but also can affect other organ systems what may lead to diseases. Some hormones can lost their function or can work more than necessary, which in both cases is cause of diseases. Adipose tissue formation is controlled by the adipose gene, which is evidence that genetics and environmental factors, also, are one of the key factors which influence mechanism of body weight control.Further will be briefly explained all those key processes which are part of mechanism of our body to work properly and ensure controlled pathways and function of organism.

2. Carbohydrate metabolism

Carbohydrate metabolism includes the various biochemical processes responsible for the formation, breakdown and interconversion of carbohydrates in living organisms.The most important carbohydrate is glucose, a simple sugar (monosaccharide) that is metabolized by nearly all known organisms. Glucose and other carbohydrates are part of a wide variety of metabolic pathways across species: plants synthesize carbohydrates from carbon dioxide and water by photosynthesis storing the absorbed energy internally, often in the form of starch or lipids. Plant components are consumed by animals and fungi, and used as fuel for cellular respiration. Oxidation of one gram of carbohydrate yields approximately 4 kcal of energy and from lipids about 9 kcal. Energy obtained from metabolism (e.g. oxidation of glucose) is usually stored temporarily within cells in the form of ATP. Organisms capable of aerobic respiration metabolize glucose and oxygen to release energy with carbon dioxide and water as byproducts. Carbohyratescan be chemically divided into complex and simple. Simple carbohydrates consist of single or double sugar units. Sucrose, table sugar is a common example of simple carbohydrates. Complex carbohydrates consist of few more sugar units. They are digested by enzymes to release the simple sugars. Starch for example is a polymer of a glucose units and it is typically broken down to glucose. Cellulose is also polymer of glucose but it cannot be digested by most organisms. Doctors and scientists want to believe that eating complex of carbohydrates instead of sugars would help to maintain lower blood glucose.Purpose of sugars is to maintain basal blood sugar, and to use those sugars for energy. Our body converts all different sugars to glucose. Common table sugar is disaccharide composed of one molecule of glucose and one molecule of fructose. Usually after eating, your blood glucose goes up, you absorb that sugar, and the more you ingest, the more your blood sugar will go up. Your body is always absorbing a sugar and liver and pancreas are two organs regulating that. Insulin is released when your blood sugar goes up. Those sugars can be stored in a form of short-term energy storage, like glycogen, which is then used by muscles to walk, to do exercises; and in form of long-term energy storage where glucose is actually converted into body fat, by process called lipogenesis. So, when you have too many carbohydrates, and when short-term storage is filled up, your body is then going to use long-term energy, and you are becoming fat. When you have carbohydrate deficit, glucagon is released, which is opposite of insulin. The more carbohydrate deficit you have, the more fat you have to burn to keep that blood sugar.Glycolysis, occurs, at least in part, in almost every living cell. This series of reactions is believed to be among the oldest of all the biochemical pathways. Both the enzymes and the number and mechanisms of the steps in the pathway are highly conserved in prokaryotes and eukaryotes. Also, glycolysis is an anaerobic process, which would have been necessary in the oxygen-poor atmosphere of pre-eukaryotic Earth. (2)Glucose metabolism is conserved throughout evolution, but species and tissue specific variations are well known and of physiological importance. The well studied metabolic pathways of glucose oxidation for energy usage are derived from biochemical studies of mammalian liver, muscle, and brain tissue as well asE.coli. The major pathways areglycolysisand thepentose-phosphate pathway producing pyruvate. Glycolysis is used by both aerobic and anaerobic organisms. Glycolysis inhumanandbacteriaare almost identical with respect to the enzymes employed, but differ by their uptake mechanism of glucose into the cell and the end product under anaerobic conditions. In humans glucose enters the cytoplasm throughglucose facilitators(passive diffusion). Inenteric bacteriaglucose intake is fueled by concomitant phosphorylation, while the hexose is transported across the membrane.Table 1.represents 10 steps of glycolysis: 1.Committed stepof glucose phosphorylation to glucose-6-phosphate- 1 ATP

2. Converting glucose-6-P into the ketose formfructose-6-phosphate

3. Phosphorylating fructose-6-phosphate tofructose-1,6- bisphosphate- 1 ATP

4. Fructose-1,6-biphosphate is split into two chemically different trioses,glycerone-P(or dihydroxyacetone-P) andglyceraldehyde-3-P(GAP)

5. Glyceron-P (DHAP) is isomerized to GAP resulting in two metabolically equivalent glyceraldehyde-3-P

6. Glyceraldehyd-3-P oxidized and phosphorylated toglycerate-1,3-biphosphate+ 2 NADH

7. Glycrate-1,3-biphosphate converted to3-phosphoglycerate+ 2 ATP

8. Phosphate at position C3 will now be moved to position C2 formingglycerate-2-P

9. Elimination reaction (-H2O) producingphosphoenolpyruvate

10. Phosphate will be transferred to form ATP andPyruvate.

The regeneration of glucose is calledgluconeogenesisand is particularly important in liver, which is the major organ involved in glucose synthesis from carbohydrateandnon-carbohydrate sources. It is the only organ that can regenerate glucose form lactate. Comparing glycolysis and its reversed mode gluconeogenesis demonstrates general rules governing metabolic pathways regarding control and reversibility. While 7 out of 10 glycolytic steps are reversible as they exhibit small change of free energy, three steps occur at a considerable larger free energy change (less than -4kcal/mol) making them irreversible. In gluconeogenesis the glycolytic enzymes are bypassed by gluconeogenetic enzymes. Table 2. Way how glycolytic enzymes are bypassed by gluconeogenetic enzymes in gluconeogenesis: ReactionGlycolytic enzymeGluconeogenetic enzyme

Glucose+glucose-6-phosphateGlucokinaseGlucose-6-phosphatase

Fructose-6-P+fructose-1,6-diPPhosphofructokinaseFructose-1,6-biphosphatase

Phosphoenolpyruvate+pyruvatePyruvatekinasePyruvatecarboxylasePhosphoenolpyruvatecarboxykinase 1

The pentose phosphate pathway is an alternative metabolic pathway for glucose oxidation in which no ATP is generated. Its principal products are NADPH, a reducing agent required in several anabolic processes, and ribose-5-phosphate, a structural component of nucleotides and nucleic acids. The pentose phosphate pathway occurs in the cytoplasm in two phases: oxidative and nonoxidative. In the oxidative phase of the pathway, the conversion of glucose-6-phosphate to ribulose-5-phosphate is accompanied by the production of two molecules of NADPH. The nonoxidative phase involves the isomerization and condensation of a number of different sugar molecules. Three intermediates in this process that are useful in other pathways are ribose-5-phosphate, fructose-6-phosphate, and gly ceraldehyde-3-phosphate. (3)

3. Lipid metabolismWe mentioned shortly in introductory part about fatty acids and their synthesis from Acetyl coenzyme A. In this part will be described in details metabolism of lipids, synthesis, breakdown, usage by other tissues etc. The mechanisms of breakdown and synthesis are regulated by different enzymes that are involved in mechanisms. However there are some another substances such as hormone insulin which stimulates fatty acid synthase expression so excess glucose will be stored as fat. In overall conversion of glucose to fatty acid there are around 25 enzymes involved. It is important to mention that enzymes are regulated by phosphorylation and by allosteric control. This is very important since high level of palmitoyl-CoA will inhibit acetyl CoA carboxylase building up of fatty acids in cell. As we saw in introduction acetyl-CoA is central molecule which can be used by different mechanisms. One portion of the acetyl-CoA is carboxylated to malonyl-CoA by acetyl-CoA carboxylase. Next, very important enzyme in this regulation is Fatty acid synthase, the main biosynthetic enzyme that performs the condensation of acetyl-CoA and malonyl-CoA to produce the 16-carbon saturated FA palmitate. ACP or Acyl Carrier Proteintransacylase is involved in activation of acetyl CoA/malonyl-CoA for reaction with malonyl ACP/acetyl ACP.Another several steps include reduction and dehydration. Reduction is when -ketoacyl-ACP reacts with NADPH + H+. The product of this reaction is 3-Hydroxyacyl ACP which enters in dehydration reaction. By removing water we get trans-2-Enyol-ACP. This molecule again is subjected to reduction and final product is Butrylyl-ACP. In reduction there is removing of double bond. Repetition of these steps six more times leads to fatty acids synthesis. By the growing of acyl-ACP molecule, replacement of the acetyl group occurs. (That is, new acetyl groups are added at the ACP end of the molecule).The product of this series of reactions, palmitoyl-ACP can be degraded to palmitate and ACP by the enzyme palmitoylthioesterase. The palmitic acid is simplest form of fatty acid. The coversion of acetyl CoA to fatty acid is also called lypogenesis, which also includes triglyceride synthesis. A triglyceride is an actually ester produced by combinig glycerol and three fatty acids. These triglycerides can be saturated (all available places where hydrogen atoms could be bonded to carbon) and unsaturated (have double bonds between carbon atoms). Once they are formed, they act as a storage form of fat in adipose tissue, and they act as a source of fatty acids needed throughout cells. Of course, diet does not provide fatty acids, but triglycerides which have to be broken down into fatty acids. If they are not required in form of fatty acids they are stored in adipose tissue or them circulating in blood. Sometimes fatty acids are needed for cell membranes, so triglycerides are present on the surfaces of cells together with enzymes lipases which breaks down triglycerides making it available for cell membrane. This was about fatty acid synthesis and mechanism how it is stored in body if it is in excess level. It is important to know that even if we are sleeping our body may have high metabolic rate. It means cells are always active performing their functions. Because of that they need constant energy. If we dont supply the energy through diet they will use alternative sources, such as glycogen (short term) and fat (long term). In comparison to other macronutrients, such as carbohydrates and proteins, fat supplies most energy in form of ATP per gram basis. The process of breakdown of triglycerides is different than synthesis. Firstly, lipolysis is process of breakdown of triglycerides into one glycerol molecule and three free fatty acids. One molecule of glycerol is used for gluconeogenesis to form glucose molecule. Free fatty acids can be very toxic so they are binding to albumin and travel through blood to final destination which is cell that requires energy for normal work. This is not just simple mechanism, but involves some hormones which trigger these pathways, but we will talk about them in another section. Recall that we said that Acetyl CoA represents central molecule which undergoes different pathways and mostly Krebs cycle. Actually, fatty acids pass through process called -oxidation in order to produce Acetyl CoA. When they get into cell they are transported into mitochondria where oxidation takes place. -oxidation is the repetitive process of cleaving 2 carbon molecules off the end of a fatty acid chain to form acetyl-CoA molecules. This process is being repeated until all of the carbons have been cleaved into 2-carbon acetyl-CoA molecules. This pathway includes several steps driven by enzymes such as shown in table 3.Table 3. List of reactions and their corresponding enzymes TYPE OF THE REACTIONENZYME INVOLVED

Dehydrogenation/oxidationAcyl-CoA dehydrogenase, yielding 1 FADH2

Hydration Enoyl-CoA hydratase

Dehydrogenation/oxidation3-hydroxyacyl-CoA dehydrogenase, yielding 1 NADH

CleavageThiolase, yielding 1 acetyl-CoA and a fatty acid that has been shortened by 2 carbons.

Newly formed molecule of Acetyl CoA now can enter Krebs cycle. For eukaryotic organisms fat is best source of energy. Saturated fatty acids yield 8.1 ATPs per one carbon. 108 ATPs are produced by simplest palmitic acid. Two of them are used so net yield is 106 molecules of ATP. This is how our body regulates the production and usage of fatty acids. Organism is perfect factory where everything is highly regulated. It requires precise usage of all substances, as well as fats. All of that is not needed immediately is stored in fat cells. Adipose tissues or fat cells are reserves of fats. Depending on cells needs and food intake this tissue sometimes is bigger or smaller. Fat is transported via blood to target cells. Lipids are not only triglycerides or fatty acids, but large and diverse class of macronutrients which includes waxes, sterols, phospholipids, fat-soluble vitamins. Although their main function is storing energy, derivate can serve as hormones, such se steroids derived from sterol lipids. We are not going to include every type of lipids in detail, but focus on more important molecules and that is cholesterol which is another name of sterol lipids. Cholesterol as molecule is very important because it is integral component of membrane, what is very beneficial for cells regarding to structural integrity and fluidity. Major dietary sources are cheese, pork, egg yolks, fish and beef. It can be synthesized by human cells, from Acetyl Co-A. Two examplesexplain how it is related to weight. Firstly it is lipid which can be stored for later usage. Another important reason is that the derivatives such as progestagens, glucocorticoids, mineralocorticoids, androgens, and estrogens. Glucocorticoids are highly related. Glucocorticoids (cortisol) promote gluconeogenesis and the formation of glycogen; enhance the degradation of fat and protein.They are present in blood, so all around body in order to be close to target cells. Since lipids are only slightly soluble in water, cholesterol (like all fat molecules) is transported around the body (in the water outside cells) inside lipoprotein particles. There are several types of particles and our interest is only two, HDL (high-density lipoprotein) and LDL (low-density lipoprotein). HDL is referred as good andLDL is referred as bad. LDL cholesterol tends to deposit in the walls of arteries. This process starts as early as childhood or adolescence. This can cause a blockage of coronary arteries so that is the reason why it is bad. HDL can transport LDL particles to the liver where it is processed. People with high body weight have high level of LDL particles, so higher risk to be affected with certain cardiovascular disease. 4. Hormones involved in mechanism of body weight controlHormones that circulate in the blood are ideally suited to act as signals between cells. Since lipid metabolism has to be coordinated with carbohydrate metabolism, same hormones also affect the synthesis, degradation, and storage of carbohydrates. Body weight regulation and energy homeostasis is controlled by a myriad of metabolic pathway intermediates and endocrine control systems. Food intake is under the control of the central nervous system through many interconnected neuroendocrine and neurotransmitter circuits.(5)Energy expenditure is regulated by the autonomic nervous system and numerous endocrine hormones, the most prominent of which are the thyroid hormone system. (6)Glucagon, epinephrine and insulin are the principal hormonal regulators of fatty acid metabolism. Insulin and glucagon are related to glucose, its production and degradation, but also together with epinephrine are principal hormone regulators of fatty acid metabolism. Glucagon and epinephrine are present in high concentrations in the fasted state and insulin is present in high concentrations in fed state. These hormones are thus key regulatory hormones involved in mechanism of body weight control. Our body is one great and perfect machine which works all the time and regulates and updates itself, and this three hormones are up to now most studied and familiar to public, but also key in synthesis and degradation not only fatty acids, but some other molecular metabolisms.From the rate of glucose in blood depends which hormones will be active and at which amount. Since glucose fluctuations are not predictable, hypoglycaemia and weight gain are common. This might be result of deficiencies or abnormalities in glucoregulatory hormones(insulin, glucagon, amylin, GLP-1, glucose-dependent insulinotropic peptide (GIP), epinephrine, cortisol, and growth hormone). Concentration of glucose is result of the amount of glucose entering the circulation which is balanced by removal of it from circulation.Glucose circulation is derived from three sources: intestinal absorption during the fed state, glycogenolysis, and gluconeogenesis.(7) Those are all part of mechanism of body weight control. Glycogenolysis and gluconeogenesis are partly under the control of glucagon, a hormone which is produced in the -cells of the pancreas. During the first 812 hours of fasting, glycogenolysis is the primary mechanism by which glucose is made available. Glucagon facilitates this process and thus promotes glucose appearance in the circulation. Over longer periods of fasting, glucose, produced by gluconeogenesis, is released from the liver.(8)Even though many tissues have ability of hydrolyizing of glycogen, only kidneys and liver contain glucose-6-phosphatase, enzyme that is necessary for releasing of glucose in the circulation. In glucose homeostasis, insulin is key regulatory hormone of glucose disappearance, and glucagon of glucose appearance. Glucagon itself is often referred as hormone that opposes effects of insulin and plays major role in sustaining plasma glucose during fasting by stimulation of glucose production on a way that, when rate of plasma glucose falls under the normal range, secretion of glucagon increases and results in glucose production and return of it to the normal value. When organism is in fed state, concentration of insulin is increased, opposite of glucagon. Primary, it signals the cells to increase their uptake of glucose. Secondly, it acts on the liver to stimulate glycogenesis. Simultaneously, insulin inhibits glucagon secretion from pancreatic -cells, thus signalling the liver to stop producing glucose via glycogenolysis and gluconeogenesis. Other actions of insulin include the stimulation of fat synthesis, promotion of triglyceride storage in fat cells, promotion of protein synthesis in the liver and muscle, and proliferation of cell growth.(9)The key regulatory enzyme for fatty acid synthesis is acetyl-CoA carboxylase. High insulin evels after a meal inhibit the hydrolysis of stored triacyglycerols and stimulate the formation of malonyl CoA by acetyl-CoA carboxylase. Malonyl CoA allosterically inhibits catnitineacyltransferase I. As a result, fatty acids remain in the cytosol rather than being transported into mitochondria for oxidation. Regulation of fatty acid synthesis and degradation is reciprocally related, with increased metabolism by one pathway balanced by decreased activity in the opposing pathway. The hydrolysis of triacylglycerols is inhibited in the fed state by high concentrations of insulin. When carbohydrate stores are depleted and insulin concentrations are low, an increased concentration of epinephrine stimulates triacyglycerol hydrolysis. Epinephrine binds to - adrenergic receptors of adipocytes leading to activation of the cAMP-dependent protein kinase A. (10)An increase in glucagon levels inactivates acetyl-CoA carboxylase. The result is increased transport of fatty acids into mitochondria and greater flux through the - oxidation pathway. The high concentrations of acetyl-CoA and NADH that are produced by fatty acid oxidation decrease glucose and pyruvate oxidation by inhibiting the pyruvate dehydrogenase complex. Thus, not only are fatty acids oxidation and storage reciprocally regulated, but fatty acid metabolism is also regulated so that storage is favoured in times of plenty and fatty acid oxidation proceeds when glucose must be spared.The ability of fatty acid derivatives to regulate acetyl-CoA carboxylase is physiologically appropriate; an increased concentration of fatty acids causes a decrease in the rate of the first committed step of fatty acid synthesis.Third, but not less important hormone is epinephrine, also known as adrenaline, which is secreted by adrenal glands. Epinephrine causes increase in heart rate, muscle, blood pressure, musclestregth and sugar metabolism. It is one of the two primary hormones that breakdown glycogen and is mainly released in response to stressful events to prepare the body for the fight or flight response.Epinephrine will bind to the receptor on the outside of a liver cell allowing occurrence of conformational change. This shape of the receptor changes and allows G protein to bind, and become active. The activation G protein causes a conformational change on the molecule causing adenylatecyclase to bind. Once adenylatecyclase has been activated ATP binds to the complex. AdenylateCyclase breaks down ATP into Cyclic AMP, which becomes the second messenger protein in this process. Cyclic AMP activates protein kinase, which activates phosphorylasecatalysing the breakdown of glycogen to glucose. (11)Interesting to mention and often forgotten in the discussion of weight loss and hormones, besides others mentioned previously, are testosterone and estrogen. Those are male and female germ hormones and their production falls with age. Male hormone, testosterone, stimulates high energy and is associated with burning of fat. Oppositely, female hormone estrogen encourages storage of fat.Many hormones play a part in weight control and our body knows how to use them and regulate processes and maintain mechanism work properly. Some of hormones interact with each other, others can be manipulated by drugs or meal planning, but the thing is, all of them are necessary for our organism, normal functioning and are key elements in maintaining mechanisms which control body weight.

5. Complex metabolic disordersTo maintain homeostasis of organism, all mechanisms have to work properly and in correlation with one another. When some part of mechanism does not work, immediately whole organisms feels the changes which are manifested mostly as diseases, more or less dangerous for life. Some of the most common diseases that occur when mechanism of body weight control does not work as it should are obesity, type 2 diabetes, cardiovascular diseases, anorexia etc. Understanding the mechanism of regulation of body weight control is very important because it can help doctors to treat obesity and also educate them. As we can see in many researches, it is established close correlation between obesity and type 2 diabetes. Obesity itself is result of combination of excessive food intake, decreased physical activity and also genetic inheritance and all those factors together on different ways causes metabolic changes and affect appearance of various diseases. Even though there is close correlation between obesity and type 2 diabetes, it does not have to be strictly true, since many patients which are obese do not have diabetes and opposite. One more interesting fact is that, slow metabolism is not cause of obesity, as many have thought. Instead, people that are suffering from obesity have much faster metabolism since their body have need for much more energy to maintain increased body mass. According to some scientific journals (12), beneficial effects of weight loss affect metabolic parameters of many diabetic patients and it is recommended for obese diabetic patients to lose weight. One of studies has shown that maintaining reduced body weight over the long term has proven to be exceedingly difficult for most people. One of the reasons for that is the body's ability to activate adaptive mechanisms that act to minimize weight loss. (13) The way how obesity affects type 2 diabetes is very interesting. When person is overweight, it stresses the enterier of individual cells, what means that overeating actually stresses network of membranes in the cell- endoplasmic reticulum (ER). When ER has more nutrients to process than it can handle, it sends out alarm signal which tells the cell to shut down insulin receptors on the cells surface what leads to insulin resistance and high concentration of glucose in the blood, which is key sign of diabetes. As mentioned previously, way how body weight is determined is according to energy intake and energy expenditure. Imbalance between those two causes change in body weight. Organisms use energy to perform work and efficiency of metabolism refers to the amount of energy an organism has to use in order to do a work. Of course, efficiency of metabolism is various among species and individuals among species. High metabolic efficiency means that individual needs less energy to perform some work than individual with low metabolic efficiency. Also, those individuals are able to preserve body weight in negative daily energy balance, but also more likely to gain weight during positive energy balance (expenditure exceeding intake and intake exceeding expenditure).Another very serious disease whose cause is overweight is cardiovascular disease. What threaten our heart health most is combination of high cholesterol, high blood pressure and high level of sugar in blood, all factors that are mentioned before and are related to mechanisms of body weight control. Our heart is major organ in our body, besides brain, that regulates flow of blood and pumps it thanks to vessels and veins. When there is too high concentration of substances in the blood, such as sugar or lipids, they can close those vessels and cause condition known as atherosclerosis. When in vessels are narrowed clots of too high amount of those substances, blood cannot flow regularly, or even be stop completely. This can cause heart attack or stroke. Other types of Cardiovascular Disease are heart failure, arrhythmia, heart valve problems, etc.One of major factor that determines metabolic efficiency and regulation of body weight is genetics. In some cases, obesity has been traced to mutations in single genes which usually code for proteins that are involved in the regulation of food intake, such as leptin (Ob). Metabolic studies of monozygotic twins have also provided compelling evidence for the role of genetics in determining the weight of body. One study examined the effects of overfeeding on weight gain in pairs of monozygotic twins.Although all of the individuals in the study consumed the same amount of calories for the same amount of time (approximately 3 months), there was a large variation in the degree of weight gain, from 8.8 to 29.3 lb, among different individuals. However, the amount of weight gain was very similar within each twin pair. The reverse also holds true. When moderately obese monozygotic twins were kept on a low-calorie diet, the amount of weight loss varied greatly among different pairs of twins. However, within each pair of twins, the amount of weight loss was quite similar. These results indicate that the body's response to changes in caloric intake is dictated at least in part by genetics.(14)Another interesting researchhas been done related to burning of fat and dieting. According to Well, according toAndrew Brown from the University of New South Wales, when you lose weight, you exhale your fat. Theirnew calculations, based on existing knowledge about biochemistry, were published in theBritish Medical Journal. (15)Excess carbs and proteins are converted into chemical compounds triglycerides (which consist of carbon, hydrogen, and oxygen) and then stored in the lipid droplets of fat cells. To lose weight, you are metabolizing those triglycerides, and that means unlocking the carbon that is stored in your fat cells.Losing 10 kilograms of human fat requires the inhalation of 29 kilograms of oxygen, producing 28 kilograms of carbon dioxide and 11 kilograms of water.

6. Therapeutic targets of mechanism of body weight controlSignificant and growing global health issues are represented by hypertension, heart failure (HF), type II diabetes mellitus, and chronic kidney disease represent, which we mentioned previously.There were unsatisfactory rates of control of blood pressure and also the unsatisfactory therapeutic efforts to prevent progression of HF, chronic kidney disease, diabetes mellitus, and their squeal. The failure of lifelong polypharmacy was collectively contributed bythe inherent complexity of drug titration, drug interactions, and both real and perceived adverse events.Therapy targeting the potentially unique contribution of autonomic imbalance is limited by the poorly tolerated systemic adverse effects of adrenergic blocking agents. Sympathetic or parasympathetic modifications have successfully used in preclinical experiments in models of these diseases to alter the time course of their progression.Renal hypertension and reduced total body noradrenaline with reduction of blood pressure after dorosalrhizotomy in rats, and muscle sympathetic nerve activity in humans after renal denervation confirm that the afferent signals from the kidney underlie some of the excessive sympathetic drive seen in these states.Adipose tissue produces a hormone leptin, which is acting as a sensor of fat mass in part of a negative feedback loop that maintains a set point for body fat stores. Flowing leptin concentrations are closely parallel to body fat stores, so that a rise in adiposity increases leptin production, thus inhibiting food suction and oppositely. By the consequence, both humans and mice with the loss of function mutations of the genes, that were inherited and which are encoding either leptin or its receptor expose severe early onset obesity. Role of the leptin is well established in rodents in the negative feedback regulation of body weight, but there remain some unresolved questions regarding its exact role in humans. Most obese individuals have high leptin levels as predicted, but they do not induce the expected loss in fat mass. There are large interindividual variations in serum leptin levels exist, independent of fat mass, in women naturally tending to have higher levels than men. Leptin's first andprimary function is not to prevent excessive weight gain, but the major physiological role of it is not as a satiety signal to prevent obesity in times of energy excess, but as a starvation signal to maintain adequate fat stores for survival during times of energy deficit. The challenge is to maintain the benefit of weight loss when it is achieved. Overweight and obese adults can benefit from interventions for weight maintenance following weight loss, which is showed by moderate quality evidence. There is no sufficient evidence of these benefits on the long-term sustainability. Childhood obesity should be a public health care or worry. Many of North American children and youth are overweight or obese, maybe one third of them. Behavioral treatments are associated with a medium effect in terms of reduced BMI or BMI z-score compared with a small effect shown by combined pharmacological and behavioral interventions.Increased risk for several conditions, including hypertension, hypercholesterolemia, diabetes mellitus, heart disease and stroke has been associated with overweight or obesity as major and most present diseases. Overweight and obesity translates into excess mortality risk, associated with the morbidity, observed even when increased weight is not associated with metabolic abnormalities. The treatment strategy was not in regard with the achievement of moderate weight loss, but it is associated with favourable clinical outcomes, including significant reduction in the incidence of type 2 diabetes, and blood pressure levels. In this article we focus on the leptin signal as an exemplary model of body weight control and we review the evidence challenging the classic view that leptin acts primarily at the ARC to control satiety through the melanocortin pathway, although we have alluded to the fact that a vast number of peripheral and central signals contribute to energy homeostasis. 7. Discussion and ConclusionWeight of body represents mass of substances found in organism. It is also the result of particular type of sum of the reactions. Weight of body can be very good indicator of individuals health. According to weight it is possible to predict or assume that some person has higher risk for cardiovascular diseases, or sleep apnea. This is when certain person has higher body mass index. There are many examples to predict something and say about certain person. This project paper gives some ideas about control of body weight. There is no specific mechanism which can be used to control weight, but rather by acting on two metabolisms we are acting on our weight. These two mechanisms are carbohydrate and lipid metabolism. Through our diet we are able to control weight of body. This is not only way. The work of human organism is very smart, meaning there is no two much waste product and everything is stored for further requirements. During hard work and exercise these storages are depleted. So by acting directly on accumulation of products of these two metabolisms we are acting on our weight. Another way to act should be focussed on hormones. Many people suffer also because of genetic disorders inheriting them from their parents. Excessive secretion of some hormone can affect body weight. Exercise and hard physical work cannot help to some people so researchers have to analyse mechanisms of hormones and ways how they act. By modifying these pathways with drugs obesity, cardiovascular disease and many others should be cured successfully. To sum up, as we could see mechanisms related to weight are very important. They play major reactions in our organism. Any disorder of these mechanisms affects body weight, whether is it obesity, anorexia or some another disease. The best way to control is to maintain the homeostasis of diet and balance between these sunstances.

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