Genetic Predisposition to Obesity

This assignment explores the connection between genetics and obesity, focusing on the presence of the A1 allele as a potential indicator for susceptibility to obesity. It delves into how this information can be used to warn patients about their predisposition to hedonic eating and suggests interventions like medication and behavioral therapy to manage the condition.

Proposal – The Genotyping in Hedonic Eating Individuals 1
Proposal – The Genotyping in Hedonic Eating Individuals
Student’s Name:
Instructor's Name:
Date:

Proposal – The Genotyping in Hedonic Eating Individuals 2
Proposal – The Genotyping in Hedonic Eating Individuals
Introduction
Food addiction is fast becoming a topic of great interest to researchers around the world,
especially, for its contribution to obesity. Food addiction includes food preference, choice,
hedonic eating, and motivation and rewards of pleasure end happiness.
The obesity epidemic is perceived in most developed countries, and this has been attributed to
the abundant presence of palatable foods. In such a scenario, the concept of hedonic eating is
becoming popular. While homeostatic eating is eating for calorific needs, hedonic eating means
the eating for the rewarding, pleasurable aspects of food (Lowe & Butryn, 2007). Hedonic eating
can be termed as food addiction (Avena, et al. 2012). Theorists say that to people indulging in
hedonic eating it is so addictive that it sometimes resembles being addicted to drugs (Ziauddeen,
2012). In turn, hedonic eating may result in obesity and weight gain in the respective individuals.
It has been proposed that emotional eating is spurred by emotion cues such as anxiety,
depression, boredom and sadness rather than being instigated by hunger. Engaging in binge or
hedonic eating, the person is trying to seek comfort or pleasure from food.
People who also have low satiety tend to gain weight with emotional eating. In severe cases, the
eating is called hedonic or compulsive eating. Hedonic eating is thus, a type of emotional eating.
Emotional eating is mostly regulated by the brain’s reward systems.
The four aspects that the brain’s reward system comprises are;
Motivation or wanting;

Proposal – The Genotyping in Hedonic Eating Individuals 3
Memory or learning;
Outcome or liking; and
Habituation or adapting.
These aspects result in the determination of how food is perceived, liked, memorized, and
forgotten or expected.
The properties such as “rewarding” of food are decided by the palatability of foods. The
palatability of the foods triggers the reward system of the brain in humans resulting in production
of feelings such as pleasure. Palatability is the overall desirability of a food decided by its
texture, flavor, and taste. Among humans, sweet and high-fat foods are normally considered
palatable. While some people like the sweet and high-fat foods to a great extent and indulge in
them excessively, not all of the human population is receptive to these tasty pleasures equally.
Genetic variations among humans determine whether they would indulge in hedonic eating or
not.
Many of the neurotransmitters including dopamine have been implicated in the rewarding
aspects of food (Cason et al., 2010; Atkinson, 2008). Dopamine is involving in modulating
rewards and is the best characterized among neurotransmitters. Johnson and Kenny (2010)
suggested a strong association between compulsive eating disorders and D2 receptor
expression.
Polymorphisms of TaqA1 have 3 allelic variants, namely, the A1/A1, A1/A2, and A2/A2.
Individuals who have at least one or two copies of the A1 allele have about 30% fewer D2

Proposal – The Genotyping in Hedonic Eating Individuals 4
receptors as compared with the individuals not possessing an A1 allele (Ritchie & Noble,
2003). There have been studies that suggest an association between alcoholism and A1 allele
(Noble, 2003).
The DRD2 gene is a prominent player in the neuronal circuits involving dopamine. Dopamine is
called the “feel good” factor. It leads people to look and seek pleasure. Depression is a condition
where dopamine is present in low levels. Various neuronal circuits including the opioid neuronal
circuit and the dopamine neuronal circuit interact to produce the reward values of a particular
food. These reward values of foods play a role in determining eating behaviors. An imbalance in
the different neuronal circuits in the brain results in emotional eating.
Among the first and foremost genes that were implicated in obesity in human beings, the DRD2
was one of them. Other sets of genes that have been implicated in human obesity are the ob,
lipoprotein lipase, and B3- adrenergic receptor.
There is a linkage disequilibrium between the Taq1 a and the intron/exon 7 alleles with a
functional allelic variant in the regulatory or promoter regions of the DRD2 gene. These
occurrences affect receptor expression. In order to compensate for the reduced inherited numbers
of DRD2, people with the A1 allele must use food as a stimulant to elevate brain dopamine
levels. The increase in dopamine further increases the stimulation of its few receptors with a
consequence of the person involved enjoying the feelings of pleasure and reward. This according
to scientists is the hypothesis and they stress that the hypothesized mechanism needs to be
validated with future research.
Thus, DRD2 Taq1A A1 allele (rs1800497) is a gene of great interest where polymorphism is
concerned.

Proposal – The Genotyping in Hedonic Eating Individuals 5
A food craving inventory is to be used in this research, which measures the cravings for
foods in obese individuals.
The FCI had been previously used by White (2002), and they found it a valid measure of
specific and general food cravings. The authors recommend the use of the FCI in research
pertaining to binge eating and obesity. Treatment studies can also makes use of the
inventory, which help to target food cravings and obesity.
The study undertaken by White and Grilo (2005) analysed the psychometric characteristics
of the FCI when used by the obese individuals with binge eating disorder and who were
seeking treatment for the same. Obese people with binge eating disorder seemed to crave
sweets to a greater degree that the other food classes.
Aim: We take the opportunity to indulge in the investigation of the association between the
DRD2 Taq A1 and obesity or food addiction.
Participants and methods
We are to recruit individuals who are obese and seeking treatment for obesity in a hospital. The
participants are to be presented with the choice of being enrolled in the research and all
participation is to be voluntary. Participants gave written informed consent. The participants are
to:
1. Undergo body composition measurements;
2. Answered food-addiction questionnaires; and
3. Undergo blood draw for genotyping; and
Body Measurements

Proposal – The Genotyping in Hedonic Eating Individuals 6
The obese individuals, who are to participate in the study, will have to report their height in
inches. Those obese indivladula who did not know their exact height are to be measured for
height in inches. Body mass index is to be calculated with the standard equation of:
BMI = weight (kg) / (height) 2 (m 2)
Body measurement is to include lean body mass, weight, and fat body mass. These body
measurements are to be made by biometrical impedance. From these, the basal metabolic rate of
the obese individuals is to be calculated. The percent body fat is to be calculated also. Weights
are also to be measured.
The Food Craving Inventory
The food craving inventory is to be administered to the obese participants as a second step in the
research methodology.
Craving, if present or not, and for different types of food are measured in the individual when
they self-report via this questionnaire. The frequency of craving over 28 days is to be rated by
participants on a Likert scale, where:
0, never;
1, rarely (once or twice);
2, sometimes;
3, often; and
4, always/almost every day).

Proposal – The Genotyping in Hedonic Eating Individuals 7
The type of food they carved for was also marked such as sweets, high fats, carbohydrate and
fast foods.
Genotyping
About 5 ml of blood is to be drawn in EDTA vacationer tubes. Buffy coat and plasma is to be
separated by centrifugation for 15 minutes. Genomic deoxyribonucleic acid or DNA is to be
obtained by isolation of the buffy coat. Genotyping of the samples is to be performed for the Taq
1A1 /A2 alleles of the DRD2 gene using an appropriate genotyping assay.
Real-time PCR is to be performed by utilizing 20 ng of the DNA and the SNP genotyping assay
mix and Taqman genotyping master mixes. The SDS 2.2.2 software genotyping program is to be
used to determine the alleles. Duplicates of each sample are to be performed.
Conclusion: The presence of at least one copy of the A1 allele is to be established in obese
participants.
This analysis helps in the establishment of the A1 allele presence in obese individuals. This
would help warning the patient that he/she would have to take remedial steps to refrain from
hedonic eating. Appropriate medicines and pharmacological agents can be prescribed to help the
person exert a control over their addiction or hedonic eating behaviors.

Proposal – The Genotyping in Hedonic Eating Individuals 8
Bibliography
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regulation: considerations for obesity pharmacotherapy. Obes. Rev. Vol. 9, pp. 108–120.
Avena, N. M, et al. 2012. Tossing the baby out with the bathwater after a brief rinse? The
potential downside of dismissing food addiction based on limited data. Nat Rev Neurosci., vol.
13, pp. 514.
Cason A. M., et al. 2010. Role of orexin/hypocretin in reward-seeking and addiction:
implications for obesity. Physiol. Behav., Vol. 100, pp. 419–428.
Johnson P. M., Kenney P. J. 2010. Dopamine D2 receptors in addictionlike reward dysfunction
and compulsive eating in obese rats. Nat. Neurosci. Vol. 13, pp. 635–641. doi: 10.1038/nn.2519.
Lowe, M. R., & Butryn, M. L. 2007. Hedonic hunger: a new dimension of appetite? Physiol
Behav. Vol. 91, pp. 432–439.
Noble E. P. 2003. D2 dopamine receptor gene in psychiatric and neurologic disorders and its
phenotypes. Am. J. Med. Genet. B. Neuropsychiatr. Genet. Vol. 116B, 103–125. doi:
10.1002/ajmg.b.10005
Ritchie T., Noble E. P. 2003. Association of seven polymorphisms of the D2 dopamine receptor
gene with brain receptor-binding characteristics. Neurochem. Res. Vol. 28, pp. 73–82. doi:
10.1023/A:1021648128758.
White, M. A., 2002. Development and validation of the food-craving inventory, Obes Res. Vol.
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Proposal – The Genotyping in Hedonic Eating Individuals 9
White, M. A., and Grilo, C. M., 2005. Psychometric properties of the Food Craving Inventory
among obese patients with binge eating disorder, Eating Behaviors, pp. 239–245.
Ziauddeen, H., Farooqi, I. S., Fletcher, P. C. 2012. Obesity and the brain: how convincing is the
addiction model? Nat Rev Neurosci. Vol. 13, pp. 279–286.