Obesity – A Multifactorial Disorder With A Genetic Basis

In past times, the genetic makeup of an individual has been said to be the main link of inheriting diseases. For some diseases, this claim may be true, however some diseases differ in the aspect as environmental factors now contribute widely to a person’s health. Obesity, a condition where a person has accumulated so much body fat to the point where his or her health is jeopardized, is a typical example of a disease with a genetic basis which is influenced by environmental factors to manifest. The following essay will elaborate further on the genes involved, its phenotypic effects and studies which prove that obesity is indeed influenced by environmental factors.

To begin with, obesity associated with monogenic factors refers to the presence of mutations in a single gene and although it mainly affects children, its frequency is very low compared with multifactorial polygenic obesity, which involves intrinsic and extrinsic factors. Among the most important genes involved in monogenic obesity are as follows: LEP (Leptin) – it is a 16-kD protein consisting of 167 amino acids and is mainly secreted from white adipose tissue. It acts on the hypothalamic portion of the brain which controls eating behaviour and regulates body weight by inhibiting food intake and stimulating energy use. Defects in leptin production cause early and severe hereditary obesity, however, studies in leptin replacement therapy have shown that treatment with recombinant human leptin normalizes eating behaviour and results in weight loss, thus preventing obesity.

Secondly, LEPR (Leptin receptor)-belongs to the family of cytokine receptors and is found in many tissues including the hypothalamus. It is through this receptor that allows leptin to bind and trigger hormone-mediated signalling. Deficiencies in LEPR have phenotypic similarities to LEP-deficient patients but cannot benefit from recombinant leptin treatment because the receptor does not respond to its ligand.

Thirdly, MC4R (Melanocortin 4 receptor)-is a G protein-coupled receptor expressed in neurons of the hypothalamus and when bound to α-MSH (melanocyte-stimulating hormone) results in the stimulation of receptor activity and suppression of food intake. Abnormalities of this receptor in humans causes hyperphagia and obesity.

Furthermore, the important genes involved in polygenic obesity are as follows: PPARG (Peroxixome proliferator-activated receptor γ)- belongs to the family of nuclear receptor that regulates the transcription of genes involved in cell growth, cholesterol and fatty acid metabolism, and adipocyte differentiation; some PPARG polymorphisms have been associated with obesity. Secondly, ADIPOQ (Adiponectin) – is the gene which codes for the hormone Adiponectin which is only produced in adipose tissue and released in plasma for distribution. Its receptors are mainly present in liver and skeletal muscle and involved in β-oxidation of fatty acids. However, levels of adiponectin are risk genotypes hence negatively associated with obesity. Thirdly, FTO (Fat-mass and obesity associated gene)- is a nuclear protein of the AlkB-related non-heme iron and 2-oxoglutarate-dependent oxygenase family that is most similar to the Escherichia coli enzyme AlkB, which can repair DNA methylation damage by hydroxylating methyl groups on the DNA leading to their removal. Hence, it is thought to act like a demethylase. In addition, FTO is highly expressed in the hypothalamic portion of the brain responsible for eating behaviour and energy balance and therefore linked to obesity.

According to a literature study conducted by Wageningen University, Netherlands (2016), it stated that there were several main factors which contributed to the increasing prevalence of obesity in the Pacific. Three of these main factors are as follows: Globalization – an increased flow of goods, people, and ideas associated with globalization have contributed to the increased cases of Non-communicable diseases such as obesity. Ever since the developing countries in the Pacific gained their independence, it has opened up to global ideas and goods which has resulted in the increase of movement of both people and goods; for example, imported high fat-content meats like corned beef, mutton flaps, chicken parts and dense simple carbohydrates like refined sugar and flour. In addition, root crops have been replaced by imported cereals and fatty imported meats have become the main sources of protein.

Moreover, the second factor linked to obesity is the changing of eating patterns. The transition from traditional foods in the Pacific such as root crops, breadfruit, banana, seafood, fresh fish, coconut products and local fruits and nuts, to refined cereals, animal products, oil, canned meats, canned fruits and vegetables and soft drinks; these foods are commonly high in fat, salt and sugar with little nutritional value. In spite of these facts, people of the Pacific still consume them in unhealthy amounts as it is convenient and cheap. At the same time, there is decline in the consumption of starchy staples and other traditional foods. Additionally, Pacific islanders choose to eat imported foreign foods rather locally produced food because of cost and availability. Furthermore, the third factor seen is physical inactivity. According to the World Health Organisation (2002), there is a decrease in the daily activity of many Pacific islanders due to the shift from agriculture-based occupations to civil servant office work and also due to the increasing use of modern technology. For example, the use of motorbikes and cars in urban areas instead of walking, and the use of motorized boats in rural areas instead of canoes. Hence, Pacific islanders being accustomed to this type of lifestyle has negatively influenced their overall health, consequently earning them a reputation of the highest number of cases of obesity in the world.

To conclude, the above essay has proven the statement “Obesity is a multifactorial disorder influenced by a mixture of genetic and environmental factors” to be true. Obesity has globally reached alarming levels and is gravely concerning government systems because of its association with other chronic degenerative diseases that are of high costs in health services. Moreover, it has also been discussed above that although monogenic obesity mainly affects children, it is less common than polygenic obesity, which involves several genes linked to obesity and their interaction with environmental factors such as globalization, changing of eating patterns and physical inactivity, all with reference to Pacific islanders.