Obesity: a Choice or ‘Fat Chance’? Dean Ashley explores the role of genetics in our lifestyle choices The world Health Organization estimates that
approximately 40% of people across the globe are now overweight or obese — a 20% increase since 1975. Obesity increases the likelihood of many other diseases including cardiovascular disease, stroke, Alzheimer’s disease, and cancer. As of 2019, obesity has overtaken smoking as the biggest cause of cancer, with Cancer Research UK stating that obesity is now more likely to be the cause of bowel, kidney, ovarian, and liver cancers than smoking tobacco. Obesity is therefore a growing global health problem, but what causes it? Obesity is driven by a combination of a lack of exercise, poor nutrition, and genetics. However, the contribution of genetics is often overlooked in comparison to the other factors. The Director of Research and Weight Stigma Initiatives at Yale University, Dr Rebecca Puhl, shows this leads to false connotations of obese individuals being lazy, weak-willed, unintelligent, and having low selfdiscipline. These stigmatisms then manifest themselves into discrimination that people justify by saying it will incentivise weight loss. Dr Puhl and others demonstrate that this is not the case. The stigmatism and prejudice are factually unfounded, reduce the mental wellbeing of sufferers, and interfere with effective treatment of the disease. Many have discovered that if we consume more food than we need, our bodies store this excess as fat. We can then use this excess energy during exercise, heat production, and resting metabolism. However, just as the amount of energy
we use for exercise differs between individuals, the energy expended during resting metabolism also differs. These differences are caused by genetics. Genes within our DNA hold the information needed for life. Genes are the template for creating messenger RNAs (mRNAs) which is then translated into amino acid sequences, known as proteins. To translate an mRNA into an amino acid sequence, ribosomes read three bases of an mRNA at a time and add a specific amino acid, corresponding to the three-base sequence, to a growing protein chain. Some individuals inherit gene mutations from their parents called single nucleotide polymorphisms (SNPs). A SNP occurs when a single base in a gene’s DNA and mRNA sequence is replaced with another. This one base change causes ribosomes to read the mRNA sequence differently and add a different amino acid into the protein chain. Sometimes this change in amino acid sequence prevents the protein from functioning correctly and can lead to diseases including obesity. Therefore, someone can inherit a variety of SNPs that predispose them to obesity from their parents. This increases the probability of an individual becoming obese and is independent of will power, intelligence, or laziness. One such SNP predisposing individuals to obesity is found in the AP-2 gene. Due to AP-2 regulating proteins involved in insulin signalling, changes to its structure can lead to insulin resistance, type 2 diabetes, and cardiovascular disease. Due to the high volume of proteins involved in regulating metabolism, the number of mutations that can
Single Nucleotide Polymorphism | (a) DNA is first transcribed into mRNA. Ribosomes translate an mRNA to produce an amino acid chain (also known as a protein) using the mRNA triple base-sequences as codes. The amino acid chain then folds into a 3D protein structure. (b) In this example, the cytosine (C)-guanine (G) base pair is mutated to a thymine (T)-adenine (A) base pair (red circle). This changes the mRNA sequence, where there is an uracil base (U) instead of a cytosine base. When a ribosome reads this mutated mRNA sequence, a different amino acid is incorporated into the amino acid chain. This change can prevent it from folding or alter its final 3D form. As a result, the protein cannot function correctly, which can predispose individuals to diseases such as obesity.
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Obesity, a Choice or 'Fat Chance'?
Michaelmas 2020
