Molecular biology and genetics student organizes scientific meetings and events for students like her to be interested in science.
Obesity is one of the most important diseases of our age that has reached pandemic proportions. Studies on certain molecular signaling pathways and tools are continuing, but research continues on whether the patient can reduce symptoms on his own and how to protect it from related diseases. Today, studies to prove the mechanisms linking obesity and cancer risk are carried out on the metabolic and endocrine effects of obesity and the changes they cause in the production of peptides and steroid hormones. In addition, obesity has been shown to contribute to the formation of many metabolic diseases, including dyslipidemia, hypertension, insulin resistance, and the inflammatory process involved in the expression of cytokines and adipokines. Understanding the effects of obesity and the link with other diseases is based on understanding which types of molecules play a role in this process. After this, understanding how the routines in our daily life are related to this disease and the effect of the change on these routines on the quality of life is one of the most important factors.
Homeostasis is the most important element for living things to survive and reproduce in their life cycle. Homeostasis is the maintenance of the regulation at the cellular level under a constant perception of balance throughout the life span of a living thing. Change necessitates evolution, and living things change parallel to the time period in which they are in the evolutionary cycle. As a result of evolution, the general understanding is that the adaptation of the living thing to its environment is based on a solid foundation. However, nature is not always in favor of living things, and from time to time, various fatal symptoms that occur as a result of the deterioration of this homeostasis play an active role in shortening the life span. Obesity, on the other hand, is a type of metabolism-centered disease that can be detected by exceeding the body mass index (BMI) that scientists are working on today, regardless of developed and underdeveloped countries. Obesity can be affected by many factors such as genetic factors, unhealthy eating habits, negative interactions with psychological factors. Adipose tissue in humans functions to store energy in the form of fat. Triglycerides are the main storage lipids. There are two main types of tissue subcutaneous (subcutaneous) and visceral (intraabdominal). Subcutaneous adipose tissue is largely defined as adipose tissue between the skin and muscle, while visceral fat is found in the main cavities of the body, particularly the abdominal cavity. Abdominal visceral adipocytes are metabolically more active than abdominal subcutaneous adipocytes, since they have conversion activity to glycerol and free fatty acids as a result of the hydrolysis of high triglycerides and release large amounts of free fatty acids (3). Another important factor in adiposity measurements is the amount and location of adipose. The values provided by these 2 factors should be especially taken into consideration (11). Definitions related to the classification and reporting of healthy weight, overweight and obesity in populations are determined with the help of anthropometry, which is historically called the branch of science that gives an idea about the physical structure of the person using body measurements rather than clinical criteria. Although obesity does not appear to have a direct effect on diseases, it has an effect on the probability of occurrence in some diseases as well as causing some disease types directly or indirectly. Some of these diseases are heart disease, stroke, diabetes and various types of cancer. (1) Obesity itself has fatal effects, and in 2017, the number of people who died prematurely due to obesity was found to be 4.7 million. These values will correspond to 4 times the number of people who died in traffic accidents and 5 times the number of people who died from HIV / AIDS in that year. (2) In another study in the same year, it was shared in the data results that the effectiveness of obesity-induced kidney and diabetes on global mortality and lifetime diseases was 83.3% per 100,000 people. Although it is known that functional capacity causes some complications in the respiratory system, mortality rate among obese patients with COVID-19 disease also increases for this reason.
In line with these results, obesity patients have a high rate of being affected by diseases associated with viral respiratory tract infections. However, although research on this topic continues, it is not yet possible to talk about a definite relationship (4). In the case of hormone-dependent neoplasms such as breast cancer, increased production of estrogenic compounds with excess fat tissue, production and secretion of secretion factors and angiogenic stimulants can contribute to tumor growth and metastasis. evaluated the relationship between and / or prognosis. Early studies have shown that the relationship between body fat index and breast cancer risk changes depending on the menopausal state, and women with a high body mass index have a higher risk of developing breast cancer after menopause.
When the molecular mechanism of obesity is examined, it has been observed that it is not possible to hold a single molecule responsible. Leptin, which is a product of the obesity gene (ob), is an important circulation signal that plays a role in the regulation of body weight in the human body. It is a 16 kDa cytokine that was discovered in 1994 as a regulator of body weight and energy balance effective in the hypothalamus. In experiments on cloning and examining this gene, it has been shown that it plays a very effective role in regulating the energy balance of our body (5). The leptin receptor is not only responsible for energy regulation, but also affects inflammatory mediators in some types of cancer and plays a role in promoting the growth of carcinogenic cells (6). However, the results of the experiments with mice used as model organisms found us that unlike mice, human obesity was associated with the development of Leptin resistance, not with Leptin deficiency. And this finding is some kind of proof that body fat is correlated with Leptin. (5) Mutations in the human ob gene are extremely rare (7). Leptin also acts as a growth factor in epithelial cells and invites the development of this many types of cancer. (8)
This information shows that leptin has many different functions. Disruption of leptin signaling can affect a variety of systems, including the cardiovascular, immune, reproductive and nervous systems. The expression of leptin in these areas suggests that leptin functions as a metabolic hormone (9). Leptin evolved as an evolutionary solution to a mammal's need to provide sufficient fat stores to survive in poor environmental caloric conditions. One way to control energy stores is to regulate nutritional behavior. Thus, the concentration of circulating leptin, which is proportional to the total adipocyte size and number, informs the brain and its nutritional circuit about the state of the stored fat. Behavioral and metabolic homeostatic processes mediated by these circuits respond to this information. At the end of the day, when we examine Leptin, we see that it plays a role in obesity, but although we want to define the relationship with cancer as benign, we certainly cannot come to a conclusion.
Adipose tissue plays an important role in the human body, balancing energy storage glucose and controlling fatty acids. At the same time, this tissue has a feature such as storing excess fat in the body. Fat stored in adipose tissue is stored in the form of lipids. In addition to storing lipids, this tissue secretes molecules that inform the organs in the brain in line with metabolic demands to the bloodstream according to the homeostasis state of the body. These molecules secreted are Adiponectins. (10) It is spoken in studies that adiponectins may play a role in cancer, but it has been observed that adiponectin levels are decreased in obese patients beyond being seen as a cause of obesity. (11) However, it has been proven by some studies that the fat accumulation caused by obesity impairs homeostasis in lipid storage and adipokine expressions and contributes to poor vascular structure in blood vessels, thus causing a negative return in heart function. (12)
Cytokines secreted by lipid tissue into the blood can also activate macrophages and other inflammatory cells in tissues. General data have shown that the accumulation of adipose tissue with macrophages during obesity is not in normal amounts. This variability at the macrophage level confirms that it contributes to tumorgenesis. Inflammation is the body's response to harmful stimuli in order to protect homeostasis. This response is also triggered by obesity, and as a result, with systemic increases in circulating inflammatory cytokines and acute phase proteins, it triggers the accumulation of leukocytes into problematic tissues, activation of tissue leukocytes and restorative tissue responses. (15) However, the nature of inflammation caused by obesity is inherent in several aspects. Obesity, which is encountered in the developmental age, may also put a lifetime risk of inflammation. In the study, C reactive protein has been identified as an important protein that plays a role in inflammation in the process of obesity in adults. However, it has been observed that this protein was detected in children over 3 years of age who later encountered obesity, and it has been proven by studies that this marker that triggers inflammation has long-term effects, and it is expressed throughout the development of children who experience obesity, and this represents a great risk for development. (16) Again, due to placental inflammation for a similar reason, inflammatory mechanisms in the mother's womb may be activated and affect fetal development. (17)
According to the studies we have, obesity is cited as the cause of 14% of cancer deaths in men and 20% of women. (18) Especially chronic subclinical inflammation, sex hormone deregulation, insulin / IGF-1 pathways and secretion of different adipokines in which leptin plays a key role. Several closely related mechanisms have been proposed to explain the relationship between breast cancer and obesity. Hyperleptinemia is one of the pathophysiological factors of breast cancer in obesity. Leptin is considered as both a hormone and adipokine. It is mainly produced and secreted by adipose tissue. It has also been found that the recurrence rate of cancer is high due to obesity in cancer survivors. Various studies have shown that insulin resistance resulting in hyperinsulinemia is associated with the emergence of breast, prostate, colon and kidney cancers. The increase in insulin, which has been observed to occur with serious problems such as cancer, has proven to increase its expression with the insulin-like receptor instead of increasing its expression per plug. (20) Studies on insulin-like growth receptor (IGF-IR) have also been observed to play a role in the development of this receptor malignant. We see that this receptor invites malignant tumors with obesity along with its resistance in the body. (19)
Behavior and Economic Impact
In the family dynamics that occur with the child, the child may tend to obesity depending on the condition that the psycho-social effects of these dynamics are positive or negative. In this process, the child is beyond the long-term impact of harmful protein buildup.
As a result of the researches on these psychological factors, a profile that is depressive rather than positive, far from developing and adopting the concept of self-confidence, withdrawn, and far from expressing the problems and thoughts he has been experienced has been observed.(25) Although the effects of emotional change and psychological conditions on life are known, it shows that an approach that aims to improve emotional regulation in both adults and children can contribute to the effectiveness of a program designed to reduce obesity, considering that it also plays a role in diseases such as obesity. If these psychological factors in children are not resolved during the growth process, we also see that they will deal with obesity in the adult stage.
All over the world, social media and TV tools have an impact on obesity and play an active role in dragging people into a sedentary life. It has been proven by studies that the time spent on these resources prevents the habits such as taking steps and doing sports during the day. (21) The consumption of products designed and designed to attract the attention of people, which are designed on the unhealthy life preferences published in these channels, and obesity caused by the intake of extra calories. danger and invites many diseases. When we look at the prices and user rates of these types of products, it is decided that healthy vegetables and fruits are sold at prices above average and that they will not damage the economic situation and because the main reason for returning to such harmful foods is cheap, obesity is unfortunately seen more in the low-income family profile, while agriculture and animal husbandry are more common in rural areas. It has been observed that obesity is less common in people who make a living with such professions because of their active lives. (22) In a study conducted on patients who survived cancer, it was observed that active living significantly reduced the rate of recurrence of cancer. (23)
In patients diagnosed with obesity, one of the things to do to prevent cancer and many other diseases is to apply a diet suitable for the profile of the patient under the doctor's control and to make an active life. It has been determined that this physical activity and diet will also restore the natural balance of structures such as insulin, leptin and adiponectin, reducing the risk of developing a better quality of life and certain disease groups and protecting the immune system. We know that the causes of obesity are not only physiological but also psychological. In order for the whole process to continue under the name of solid foundations, it is important that the patient continues in this process with the help of psychologists.
The data we have show us that obesity is affected by many factors such as environmental conditions, nutritional habits, psychological status, genetics. As a result of more detailed studies, we see that the expressions of some molecular mechanisms that cause cancer are affected abnormally due to obesity and that molecules of obesity origin play a role in the mechanism of many diseases other than cancer. At the same time, it is accepted that obesity is also seen in children, unlike the gender distinction, and that this situation is a worrying topic for future generations, but if we impose habits that will prevent obesity into our lives, it will protect us against all these risks. Studies on the therapeutic effects that may occur as a result of targeting specific kinase pathways in current studies are ongoing.
1-WHO (2018) – Fact sheet – Obesity and overweight. Updated February 2018.
2-doi: 10.1371/journal.pmed.1003198 The global burden of disease attributable to high body mass index in 195 countries and territories, 1990–2017: An analysis of the Global Burden of Disease Study
3-Rose DP, Vona-Davis L. Biochemical and molecular mechanisms for the association between obesity, chronic inflammation, and breast cancer. Biofactors. (2014) 40:1–12. doi: 10.1002/biof.1109
4-Obesity and COVID-19 Severity in a Designated Hospital in Shenzhen, China
Qingxian Cai, Fengjuan Chen, Tao Wang, Fang Luo, Xiaohui Liu, Qikai Wu, Qing He, Zhaoqin Wang, Yingxia Liu, Lei Liu, Jun Chen, Lin Xu
Diabetes Care Jul 2020, 43 (7) 1392-1398; DOI: 10.2337/dc20-0576
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7- Boden, G., X. Chen, M. Mozzoli, ve I. Ryan. 1996. “Effect of fasting on serum leptin in normal human subjects”. Journal of Clinical Endocrinology and Metabolism.
8- Hardwick JC, Van Den Brink GR, Offerhaus GJ, Van Deventer SJ, Peppelenbosch MP. Leptin is a growth factor for colonic epithelial cells. Gastroenterology. 2001 Jul;121(1):79-90. doi: 10.1053/gast.2001.25490. PMID: 11438496.
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10-Khandekar, M. J., Cohen, P., & Spiegelman, B. M. (2011). Molecular mechanisms of cancer development in obesity. Nature Reviews Cancer, 11(12), 886–895. doi:10.1038/nrc3174
11- . Hu, E., Liang, P. & Spiegelman, B. M. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J. Biol. Chem. 271, 10697–10703 (1996)
12-Epicardial Adipokines in Obesity and Coronary Artery Disease Induce Atherogenic Changes in Monocytes and Endothelial Cells Kalypso Karastergiou, Ian Evans, Nicola Ogston, Nazar Miheisi, Devaki Nair, Juan-Carlos Kaski, Marjan Jahangiri, and Vidya Mohamed-Ali Originally published15 Apr 2010https://doi.org/10.1161/ATVBAHA.110.204719Arteriosclerosis, Thrombosis, and Vascular Biology. 2010;30:1340–1346
13-J. Clin. Med. 2021, 10(1), 56; https://doi.org/10.3390/jcm10010056vReceived: 9 December 2020 / Revised: 21 December 2020 / Accepted: 23 December 2020 / Published: 26 December 2020
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15-Inflammatory links between obesity and metabolic disease Carey N. Lumeng1,2 and Alan R. Saltiel2,3,4 Published June 1, 2011
16-Multiple markers of inflammation and weight status: cross-sectional analyses throughout childhood Asheley Cockrell Skinner 1, Michael J Steiner, Frederick W Henderson, Eliana M Perrin Affiliations expand PMID: 20194272 PMCID: PMC2909480 DOI: 10.1542/peds.2009-2182
17-Frias AE, et al. Maternal high–fat diet disturbs uteroplacental hemodynamics and increases the frequency of stillbirth in a nonhuman primate model of excess nutrition. [published online ahead of print March 29, 2011]. Endocrinology. doi:10.1210/en.2010-1332.
18-Oncologist. 2010 Jun; 15(6): 556–565. Published online 2010 May 27 doi: 10.1634/theoncologist.2009-0285 PMCID: PMC3227989 PMID: 20507889 Obesity and Cancer Kathleen Y. Wolin,corresponding authora,b Kenneth Carson,b,c and Graham A. Colditzac
19-Frasca F, Pandini G, Sciacca L, Pezzino V, Squatrito S, Belfiore A, Vigneri R. The role of insulin receptors and IGF-I receptors in cancer and other diseases. Arch Physiol Biochem. 2008 Feb;114(1):23-37. doi: 10.1080/13813450801969715. PMID: 18465356.
20-Belfiore A. The role of insulin receptor isoforms and hybrid insulin/IGF-I receptors in human cancer. Curr Pharm Des. 2007;13(7):671-86. doi: 10.2174/138161207780249173. PMID: 17346183.
21- Bennett GG, Wolin KY, Viswanath K, Askew S, Puleo E, Emmons KM. Television viewing and pedometer-determined physical activity among multiethnic residents of low-income housing. Am J Public Health. 2006 Sep;96(9):1681-5. doi: 10.2105/AJPH.2005.080580. Epub 2006 Jul 27. PMID: 16873736; PMCID: PMC1551955.
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24- Renehan AG, Tyson M, Egger M et al. Body-mass index and incidence of cancer: A systematic review and meta-analysis of prospective observational studies. Lancet 2008;371:569–578.
25- Fabricatore AN, Wadden TA. Psychological aspects of obesity. Clin Dermatol. 2004;22:332–7.
26- Casagrande, M., Boncompagni, I., Forte, G. et al. Emotion and overeating behavior: effects of alexithymia and emotional regulation on overweight and obesity. Eat Weight Disord 25, 1333–1345 (2020). https://doi.org/10.1007/s40519-019-00767-9
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