Obesity Genetics and Lifestyle - Essay Example

?Introduction Obesity accounts for a considerable amount of cost in total health expenditure because of the relative increase in health care cost (Alter et al, 2012, p.1). Obesity is associated with development of diabetes and other cardiovascular diseases since studies suggest that accumulation of fat in the abdomen poses great risks compared to subcutaneous fat (Alter et al, 2012, p.1; Stryjecki&Mutch, 2011, p.286-7). Obesity results from complex interactions like multiple behavioural, biological as well as environmental factors that significantly affect long-term livelihood (Lu, & Young Ae, 2008, p.684-687). Occurrence of obesity is high; although, there are differences in the level of obesity as well as the rates of increase. Figure 1 Typical body shape corresponding to the Body Mass Index (Diet Calculator) Lifestyle factors such as physical activity together with dietary intake are associated with obesity in children in various nations across the globe (Katzmarzyk et al 2013, p.1). The past few decades have witnessed epidemic increase of obesity in societies where the environment provides calorie-rich foods accompanied by little physical activity. Even though, alterations in genetic makeup take place at a slow pace to be responsible for the increase in obesity, genes do have a role in development of obesity (CDC, 2010). This is likely because genes regulate the way a body captures stores and releases energy from food; therefore, any explanation regarding obesity has to incorporate the role of genetics (CDC, 2010). Obesity genetics and lifestyle According to Kopelman, Caterson and Dietz, (2010), studies suggest that development of obesity entails hormones and neurotransmitters like leptin and ghrelin that control appetite with the hormones acting on certain centres within the brain in order to regulate sensations of satiety. Therefore, mutation of these hormones and even their receptors can result in obesity; as well, biochemical pathways in organs that have been implicated in pathology of obesity. Obesity is a condition where the body fat accumulates with time due to chronic imbalances in energy since the amount of calories taken exceeding the amount of calories expended. Even though, genes may not be entirely accountable for the increased obesity, genetic inclination plays a significant role in development of obesity. Genetic factors account for more than 40% of BMI variations within a population because genes affect the way the body captures, stores and even releases energy from food (Cheung &Peizhong, 2012, p.1-2). One intriguing explanation for the increase in obesity is the mismatch between the current environment and “energy thrifty genes” that increased in the past in different environmental conditions when sources of food were scarce (PR, 2013). “Thrifty genotype” theory still remains in the spectrum where genes support accumulation of fat within a certain environment. The ways that contribute to obesity include desire to overeat, inclination to be sedentary, diminished ability to use dietary fats as fuel that enlarge the stimulated capacity to store body fat. The differences in the way people react to similar ecological conditions offer a suggestion that genes have a significant role in developing obesity (Plos Biology, 2005). Genetic contribution to common obesity is established through adoption, family and twin studies with twin studies showing that genetic factors can contribute to more than 40% in BMI variation while low heritability is visible in families and adoption at a rate that is less than 20% (Cheung &Peizhong, 2012, p.2; Naukkarinen et al, 2012, p.1017). The latest update on the human obesity gene map indicates127 candidate genes for obesity related traits; moreover, a large-scale study suggests obesity to be strongly associated with genetic variants within the melanocortin-4 receptor gene. According to Jelalian and Steele (2008), recent genome-wide association studies offer evidence that certain genes may contribute to obesity in both children and adults. The positive associations in the genome-wide association identified replication in adults and children where C allele got transmitted to overweight children, which points that genome screening offer reasonable basis for recognising genes responsible for obesity (Jelalian and Steele (2008, p.166). Moreover, other genes including prohormone convertase gene, brain-derived neurotrophic factor gene as well as the endo-cannabinoid receptor 1 gene are evident in common obesity (Yeo&Heisler, 2012, p.1343; Adan et al, 2006, p.815; Fernandez, Klimentidis, Dulin-Keita &Casazza, 2012, p.480). The significance of the renowned genes confers to obesity increase. Hypothalamic leptin-melanocortin system is essential in balancing the energy in humans since interference of the network causes obesity phenotypes (Cheung &Peizhong, 2012, p.2-3). Heritable factors are known to explain many variations on the risks regarding obesity; nevertheless, these genetic factors explain small ratio of the risk (Wardle, 2009, p.997). Obesity being a complex problem for scientists makes scientists struggle to understand it because in some cases, genetics are considered to be responsible and as well the various combinations metabolic and behavioural factors seem to play a significant role (“Obesity in America” 2012, p.5). The reduction of physical activity does not necessary lead to increased weight if it was not offset by the increase of leisure time. Sedentary work is an inevitable product within the information age that involves watching TV, which involves watching advertisements of junk foods that are readily available. Sedentary work and static recreation account for a huge portion of obesity as well as the modern eating that contributes to the development of obesity. This trend seems to be propelled by social influences; even though, doctors and nutritionists and other experts advocate for prudent eating and regular exercising the influences of food and entertainment industries seem to push back with appealing adverts that trash sombre warnings (“Obesity in America” 2012, p.7). Through various peptides secreted within the body, appetite is influenced by the activities in hypothalamus as well as the autonomic nervous system (van Vliet-Ostaptchouk et al, 2009, p.593). The hormones originate from various sites that include fat cells, the endocrine pancreas and the gastrointestinal tract (Coll, Farooqi and O’Rahilly, 2007). Genome-wide association (GWA) studies resulted in the expansion of loci associated with various polygenic diseases like obesity. Since its establishment, GWA has developed in various ways one of which comprised studies that confirmed FTO (Fat mass and Obesity-associated genes) as the first gene that is incontrovertibly associated with obesity and related traits. Thus, through introduction of genome-wide association approach, there have been fruitful discoveries based on high-density genome-wide association studies for obesity-related traits. Genetic alterations that include mutations explain a limited portion of obesity because it is well known that dietary habits and lack of exercise play a huge role in the development of obesity. Dietary factors can alter body weight and obesity and although there is concern regarding the role of sugar in obesity and metabolic syndrome, there is little controversy regarding the influence of fructose on obesity and metabolic syndrome (Cheung & Peizhong 2012, p.7). Consumption of too much fructose may be associated with diabetes, metabolic syndrome and obesity; although long-term effects are inadequately explored in humans. Increased use of high-fructose foods mirrors the increased prevalence of obesity; as well, increased fructose predisposes people to obesity because it does not stimulate release of insulin. Insulin, leptin and ghrelin regulate intake of food as well as the prolonged energy balance through the nervous system. Insulin stimulates leptin while suppressing ghrelin; hence, the high-fructose foods significantly decrease circulation of insulin and leptin while increasing ghrelin concentration that enhances hunger and increases caloric intake (Haneline & Meeker, 2011). Childhood obesity results from complex interactions of various behavioural, genetic and ecological factors that significantly affect long-term energy balance (Pomp, Nehrenberg and Estrada-Smith, 2008 p.331). Of concern is that behaviours like physical activity and dietary intake are associated with obesity in children in various nations although the extent of the different lifestyles on obesity in children differs with region (Katzmarzyk et al 2013). Genes as well as the environment influence eating behaviours that result in obesity because the ability to be sensitive to certain compound together with the food environment strongly influences obesity in children. Obesity and genetics According to Watson (2009), as scientists learned from related groups, obesity tends to run in families; thus, if an individual has a family history of obesity then the individual is 2 to 3 times likely to be obese compared to an individual without a family history in obesity. Therefore, an individual chance of being overweight is high if one or both of the individual’s parents are have obesity (Barness, 2007, p.76). Genes influence a person’s weight in various like altering the way the body responds to hormone leptin, which makes an individual feel hungry even if the individual ate enough. Genes can influence an individual’s taste buds, making the person prefer sweet and fatty foods compared to healthy foods; for instance, genes like 6-n-propylthiouracil (PROP), in certain people allows the individuals to taste bitter substances, which are found in certain vegetables making the individual avoid taking healthy vegetables (Watson, 2009, p.36; Lillycrop & Burdge 2011, p.72-3). Moreover, genes have the ability to affect metabolism in people, which in return slows the rate cells burn energy from food; hence, the individual stores the energy in the form of fat; as well, genes influence where the body stores the fat. According to Yeo and Heisler (2012, p.1343), many of the single-gene cases involve melanocortin 4 receptor genes that are used in coding the protein involved in feedback loop that signals to the hypothalamus indicating that the body is full (Stutzmann et al, 2009, p.373). Therefore, when the gene is faulty, message gets confused enabling people to continue eating because they feel that they are hungry. Nevertheless, regardless of the influence of genetics on obesity, environmental determinants play a significant role in obesity (Watson, 2009, p.37-39). Increased prevalence of obesity is a reflection of secular changes in both environmental and lifestyle factors because of the increased intake of nutrient-dense foods together with decreased physical activity. Familial studies suggest involvement of genes in obesity, which is in line with a certain degree of degree of genetic influence on BMI (Body Mass Index) and predisposition to obesity (Rokholm et al, 2011, p.1). Other obesity related traits like the measure of the distribution of fat are heritable although this trait is high in women; hence, the traits shows sex specific gene influence (Grant, 2014, p.34). Genetics play a causative role in few cases of obesity; although, in most cases obesity never stems from a single gene in development of obesity (Farooqi & O'rahilly, 2005, p.444). Apart from MC4R, which makes individuals feel hungry and overeat causing obesity, GWA studies have come up with various genes linked to obesity some of which have little influence; besides, other genes include Leptin receptor, leptin and FTO. Research on adopted children indicates that adopted children tend to have similar weight to their biological parents compared to adoptive parents and studies in twins yield the same results. The findings suggest the significant role of genetics in determining an individual’s predisposition to obesity. Therefore, genes interact with the diet as well as activity patterns that result in obesity and metabolic pathways that affect satiety and energy balance (Rolfes, Pinna & Whitney, 2009, p.274; Blundell, 2011, p.358). According to Rolfes et al (2009, p.274), researchers examine human genome in looking genetic answers to obesity with research studies involving proteins that are capable of explaining appetite control and energy regulation as well as obesity development. Leptin Researchers have established a gene responsible for obesity known as ob, which is expressed in the adipose tissue and codes protein leptin. Leptin usually acts as a hormone within the hypothalamus (Farooqi, 2011, p.453; Wells, & Siervo, 2011). Change in energy expenditure reflects not only the change in basal metabolism but also includes changes in physical activity patterns (Walley, Asher & Froguel, 2009, p.432). Moreover, leptin released from stomach cells when responding to the presence of food suggest the role of both short-term and long-term regulation of food intake as well as energy storage. Figure2. Leptin influence on hypothalamus and its impact on intake of food and fat metabolism (Friedman & Halaas, 1998) Although it is rare, hereditary deficiency in leptin or the genetic transformation of its receptor was established in human beings (Franks, 2006, p.527). People that are extremely obese have barely detectable blood levels of leptin, which means they have little appetite control because they are always hungry and consume more compared to their peers (Rolfes, Pinna & Whitney, 2009, p.274-275). However, when injected with leptin, the individuals lose a considerable amount of weight, which serves to show leptin’s role in controlling appetite and body weight. Injections of Leptin is efficient in repressing appetite that consequently supports loss of weight in case of overeating and being obese because of the deficiency of leptin. Besides, few obese individuals have leptin deficiency because in some cases leptin level increase together with BMI. Leptin increases but is unable to suppress appetite or even enhance energy expenditure a condition known as leptin resistance. Excessive use of fructose tends to stimulate leptin resistance and increases the storage of fat. Other studies reexamine evidence of leptin from a different perspective of under nutrition instead of focusing on its satiety level that helps in preventing obesity through diminishing appetite. When intake of energy is low, leptin levels decrease and slows metabolism in order to decrease energy demands; hence, leptin plays a significant role in regulation of energy. In addition to leptin, adipose tissue produce a different protein referred to as adiponectin and unlike leptin the protein relates inversely to body fat. Adiponectin and Ghrelin Hormone Adiponectin is secreted by adipocyte and increases sensitivity of the body to insulin. Adiponectin is high in lean people compared to people who are obese, which explains connections between obesity and other diseases like diabetes. Thus, researchers are hopeful that increase of adiponectin level may help decrease risks associated with obesity like type 2 diabetes and cardiovascular disease (Rolfes, Pinna & Whitney, 2009, p.275; Aisbitt 2007, p.184). Moreover, another protein referred to as ghrelin works in the same way as a hormone within the hypothalamus; however, unlike leptin or adiponectin, it is secreted by the stomach cells and induces positive energy balance through stimulation of appetite and promotion of efficient energy storage (Hochberg & Hochberg, 2010). Nevertheless, according to Whitney and Rolfes (2011 p.275), the role of ghrelin in regulating intake of food and body weight is subject to intense research. Ghrelin activates the desire to eat and its levels in the blood increase before and fall following a meal in proportion to the amount of calories ingested, which reflect the hunger and satiety before and after eating (Gueorguiev et al 2009, p.3; van Vliet-Ostaptchouk et al, 2009, p.593-4). Figure 3 Ghrelin secretions and feedback mechanism (Gueorguiev et al 2009). Fasting blood level inversely relate to the body weight because lean people have high levels of ghrelin while obese individuals show low levels of the protein. Therefore, ghrelin fights to uphold a stable body weight because some studies speculate that ghrelin’s role involves maximizing fat stores in periods of famine (Whitney & Rolfes, 2011 p.275). According to Whitney and Rolfes (2011 p.276), some studies indicate that ghrelin enhances sleep. Interestingly, absence of sleep promotes ghrelin, which is a hunger hormone and reduces satiation hormone leptin, which can clarify epidemiological support that links short-sleep duration to high BMI. Nevertheless, Rolfes, Pinna and Whitney (2009, p.276), indicate that scholars are attempting to comprehend the relationships among genes, eating habits, sleep disorder and various factors that affect body weight as well as weight gain. Moreover, appetite-regulating hormone ghrelin PYY levels decrease as a response to the high levels of PYY, a peptide secreted by GI cells after a meal in a proportion similar to the amount of calories ingested. According to Whitney and Rolfes (2011 p.276), a study on individuals given PYY and later offered buffet meals ate fewer calories by 30% compared to the control group. Unlike to hormone leptin that reduces food intake, PYY seems to be an efficient treatment for obesity. An ideal diet sustains satiating hormones like leptin, PYY and Cholecytokinin and decreases appetite stimulating hormone ghrelin (Little et al, 2005, p297-8). Moreover, genes code for proteins involved in energy metabolism and are capable of influencing the storage or use of energy with different efficiencies in different forms of fat like white or brown fat. Uncoupling proteins are active not only in brown fat, but also in white fat as well as other tissues and their action seem to affect basal metabolic rate and challenges the development of obesity. Animals that have large amounts of the uncoupling proteins resist gaining of weight while those with minimum amounts are capable of gaining weight easily. As well, individuals, that have generic variant of the uncoupling protein decreases metabolic rate; hence, the individuals tend to be overweight compared to others (Farooqi & O'Rahilly, 2007, p.38). Conclusion There is genetic evidence for the critical role of various proteins like leptin, ghrelin and adiponectin and its pathways that control food intake. The presence of distinct profile of appetite control in high fat and low fat indicate the various physiologic patterns response to ingested food. The various studies indicate that meal termination and post meal inhibition of appetite operate with different levels of fat. Leptin and the various other genes demonstrated the ability to control appetite and size of body, which not only relies on human choice but also on genetically based processes that regulate intake of food as well as the drive to eat. Moreover, from the study it is clear that environmental factors together with genetic factors interact in creating epigenetic that offer improved the understanding of obesity and its related diseases. The study clearly indicated that genes are capable of influencing eating behaviors because food and activity behaviors affect genes responsible for regulating the body weight. Moreover, social relations also influence development of obesity because through social interactions and individual can be induced with practices that lead to obesity. It has been clear that obesity results from various causes in people such as overeating and physical inactivity that are within a person’s control and other causes like genetics that are beyond control of an individual. References 'A Genetic Link to Obesity: The Numbers Don't Add Up for GAD2' 2005, Plos Biology, 3, 9, p. 1519. Adan, R, Tiesjema, B, Hillebrand, J, la Fleur, S, Kas, M, & de Krom, M 2006, 'The MC4 receptor and control of appetite', British Journal Of Pharmacology, 149, 7, pp. 815-827. Aisbitt, BB 2007, 'Obesity – should we blame our genes?',Nutrition Bulletin, 32, 3, pp. 183-186, Alter, D, Wijeysundera, H, Franklin, B, Austin, P, Chong, A, Oh, P, Tu, J, &Stukel, T 2012, 'Obesity, lifestyle risk-factors, and health service outcomes among healthy middle-aged adults in Canada', BMC Health Services Research, 12, 1, pp. 238-249. Barness, LA 2007, 'OBESITY IN CHILDREN', Fetal & Pediatric Pathology, 26, 2, pp. 75-85. Blundell, JE 2011, 'Physical activity and appetite control: can we close the energy gap?',Nutrition Bulletin, 36, 3, pp. 356-366. CDC, 2010, Obesity & Genetics.Center for Disease control and prevention.viewed 3 December 2013 from http://www.cdc.gov/features/obesity/ Cheung, W, &Peizhong, M 2012, 'Recent Advances in Obesity: Genetics and Beyond', ISRN Endocrinology, pp. 1-11. Coll A. P., Farooqi S. I and O’Rahilly S. 2007, ‘Hormonal Control of Food intake’129(2): 251-262. Farooqi, I 2011, 'Genetic, molecular and physiological insights into human obesity', European Journal Of Clinical Investigation, 41, 4, pp. 451-455. Farooqi, I, &O'rahilly, S 2005, 'MONOGENIC OBESITY IN HUMANS', Annual Review Of Medicine, 56, 1, pp. 443-C-1. Farooqi, I, &O'Rahilly, S 2007, 'Genetic factors in human obesity',Obesity Reviews, 8, pp. 37-40. Fernandez, J, Klimentidis, Y, Dulin-Keita, A, &Casazza, K 2012, 'Genetic influences in childhood obesity: recent progress and recommendations for experimental designs', International Journal Of Obesity, 36, 4, pp. 479-484. Franks, S 2006, 'Genetic and environmental origins of obesity relevant to reproduction', Reproductive Biomedicine Online (Reproductive Healthcare Limited), 12, 5, pp. 526-531. Friedman, J. M. & Halaas, J. L. Leptin and the regulation of body weight in mammals. Nature 395, 763–70 (1998). Grant S. F.(2014). The Genetics of Obesity.New York, NY, Springer New York. Gueorguiev, M, Lecoeur, C, Benzinou, M, Mein, C, Meyre, D, Vatin, V, Weill, J, Heude, B, Grossman, A, Froguel, P, &Korbonits, M 2009, 'A Genetic Study of the Ghrelin and Growth Hormone Secretagogue Receptor ( GHSR) Genes and Stature', Annals Of Human Genetics, 73, 1, pp. 1-9. Haneline, M. T., & Meeker, W. C. (2011). Introduction to public health for chiropractors. Sudbury, Mass, Jones and Bartlett Publishers Hochberg, I, & Hochberg, Z 2010, 'Expanding the definition of hypothalamic obesity', Obesity Reviews, 11, 10, pp. 709-721. Jelalian, E., & Steele, R. G. (2008). Handbook of childhood and adolescent obesity. New York, NY, Springer Science+Business Media. http://public.eblib.com/EBLPublic/PublicView.do?ptiID=417511.. Katzmarzyk, P, Barreira, T, Broyles, S, Champagne, C, Chaput, J, Fogelholm, M, Hu, G, Johnson, W, Kuriyan, R, Kurpad, A, Lambert, E, Maher, C, Maia, J, Matsudo, V, Olds, T, Onywera, V, Sarmiento, O, Standage, M, Tremblay, M, & Tudor-Locke, C 2013, 'The International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE): design and methods', BMC Public Health, 13, 1, pp. 1-13. Keller, K. 2008. Encyclopedia of obesity. Volume 1, Volume 1. Los Angeles, Sage Publications. Kopelman, P. G., Caterson, I. D., & Dietz, W. H. 2010.Clinical obesity in adults and children.Chichester, West Sussex, Wiley-Blackwell. Lillycrop, K, &Burdge, G 2011, 'Epigenetic changes in early life and future risk of obesity', International Journal Of Obesity, 35, 1, pp. 72-83. Little, T, Horowitz, M, &Feinle-Bisset, C 2005, 'Role of cholecystokinin in appetite control and body weight regulation', Obesity Reviews, 6, 4, pp. 297-306. Loos, RF 2009, 'Recent progress in the genetics of common obesity', British Journal Of Clinical Pharmacology, 68, 6, pp. 811-829. Lu, Q, & Young Ae, C 2008, 'Gene-environment interaction and obesity', Nutrition Reviews, 66, 12, pp. 684-694. Naukkarinen, J, et al. 2012, 'Causes and consequences of obesity: the contribution of recent twin studies', International Journal Of Obesity, 36, 8, pp. 1017-1024. 'Obesity in America: What's driving the epidemic?' 2012, Harvard Men's Health Watch, 16, 7, pp. 5-7. O'Rahilly, S, &Farooqi, I 2008, 'Human obesity as a heritable disorder of the central control of energy balance', International Journal Of Obesity, 32, pp. S55-S6. Pomp, D, Nehrenberg, D, & Estrada-Smith, D 2008, 'Complex Genetics of Obesity in Mouse Models', Annual Review Of Nutrition, 28, 1, pp. 331-345. PR, N 2013, 'Genetic mutation linked to severe obesity', PR Newswire US, 18 July, Regional Business News. Rokholm, B, Silventoinen, K, Angquist, L, Skytthe, A, Kyvik, K, &Sorensen, T 2011, 'Increased Genetic Variance of BMI with a Higher Prevalence of Obesity', Plos ONE, 6, 6, pp. 1-8. Rolfes, S. R., Pinna, K., & Whitney, E. (2009).Understanding normal and clinical nutrition. Australia, Thomson Wadsworth. Saey, T 2012, 'Genes link childhood growth and adult obesity', Science News, 182, 12, p. 13. Stryjecki, C, &Mutch, D 2011, 'Fatty acid-gene interactions, adipokines and obesity', European Journal Of Clinical Nutrition, 65, 3, pp. 285-297. Stutzmann, F, Cauchi, S, Durand, E, Calvacanti-Proenca, C, Pigeyre, M, Hartikainen, A, Sovio, U, Tichet, J, Marre, M, Weill, J, Balkau, B, Potoczna, N, Laitinen, J, Elliott, P, Jarvelin, M, Horber, F, Meyre, D, &Froguel, P 2009, 'Common genetic variation near MC4R is associated with eating behaviour patterns in European populations', International Journal Of Obesity, 33, 3, pp. 373-378. vanVliet-Ostaptchouk, J, Hofker, M, van der Schouw, Y, Wijmenga, C, &Onland-Moret, N 2009, 'Genetic variation in the hypothalamic pathways and its role on obesity', Obesity Reviews, 10, 6, pp. 593-609. Walley, A, Asher, J, &Froguel, P 2009, 'The genetic contribution to non-syndromic human obesity', Nature Reviews Genetics, 10, 7, pp. 431-442. Wardle, J 2009, 'Current issues and new directions in Psychology and Health: The genetics of obesity-What is the role for health psychology?',Psychology & Health, 24, 9, pp. 997-1001. Wardle, JJ 2007, 'Eating behaviour and obesity', Obesity Reviews, 8, pp. 73-75. Watson, S. (2009). The genetics of obesity. New York, Rosen Central. Wells, J, &Siervo, M 2011, 'Obesity and energy balance: is the tail wagging the dog?',European Journal Of Clinical Nutrition, 65, 11, pp. 1173-1189. Whitney, E. N., &Rolfes, S. R. (2011).Understanding nutrition. Australia, Wadsworth, Cengage Learning. Yeo, G, &Heisler, L 2012, 'Unraveling the brain regulation of appetite: lessons from genetics', Nature Neuroscience, 15, 10, pp. 1343-1349. Read More