Basic and Genetic Aspects of Food Intake Control and Obesity: Role of Dopamin Receptor D2 TaqIA Polymorphism

Abstract

Regulation of food intake, energy expenditure and store are strikingly linked to obesity. Homeostatic control of food intake, hunger and satiety involves adipose and gastrointestinal hormones, such as leptin, insulin and ghrelin, which eventually affect neuronal signaling in the hypothalamus arcuate nucleus. On the other hand, hedonic control of food intake relates to substances such as opioids, endocannabinoids, gamma-aminobutyric acid, serotonin and dopamine, which act on the motivation and reward mechanisms. Dopamine is a precursor of noradrenaline and adrenaline and modulates a number of physiological functions, such as appetite, depending on the brain area and the type of receptor stimulated. It has been established as the main neurotransmitter of the hypothalamic reward system. Beyond the homeostatic and hedonic energy balance control, genetic aspects are also tightly involved in obesity pathophysiology. In this context, some Single Nucleotide Polymorphism (SNP) has been linked to common obesity. Here, we highlight the role of the dopamine receptor D2 gene TaqAI polymorphism, which affects the D2 receptor availability and has been associated to obesity. Therefore, the aim of this mini review is to cover basic aspects of food intake, energy balance, dopamine-related aspects, including genetic ones, and the relation with obesity.

The Role of Genetics in the Pathophysiology of Obesity: A Systematic Review

“…It is postulated that the genes that compose the " thrifty genotype" are responsible for: higher capacity to accumulate energy in the form of fat, ability to save energy in critical periods, ability to "turn off " non-essential metabolic pathways and ability to ingest large amounts of food whenever these are available. 10,11 The same "thrifty genotype" is currently disadvantageous because of easy access to high densely energetic foods and low caloric expenditure. 9…”

“…The theory suggests that the initial genetic network responsible for low weight and high body performance characteristics has been suppressed and lost over the millennia. 11…”

“…Monogenic obesity disorders are a heterogeneous group of rare conditions that increase food intake and reduce energy expenditure. 16 Many occur from mutations in genes related to the hypothalamic system of energy balance control, 8,11,16,17 as the leptin-melanocortin system. These mutations result in changes in the concentrations and/or activity of hormones, receptors and enzymes, leading to the phenotype of intense hyperphagia with early-onset obesity, sometimes associated with endocrine abnormalities.…”

Analysis of Factors Associated with Outcomes of Bariatric Surgery: rs1800497 ANKK1, rs1799732 DRD2 Genetic Polymorphisms, Eating Behavior, Hedonic Hunger, and Depressive Symptoms

“…Speci cally, the ANKK1 TaqIA (rs1800497) polymorphism consists of a single cytosine (C, A2 allele) to thymine (T, A1 allele) change, which causes a glutamine to lysine substitution. This single nucleotide polymorphism (SNP) affects dopamine receptor availability (19), which has been associated with the risk of alcohol dependence and severe alcoholism (20)(21)(22), and to date, ANKK1 TaqIA is considered a current marker for addictive disorders (23). Some studies report an association between TaqIA polymorphisms and obesity, body mass index and food intake (12,24,25).…”