DRD2: Bridging the Genome and Ingestive Behavior

DA integrates metabolic signals with circuits regulating behavior. The Ankk1 and Fto gene variants interact to influence DA-dependent functions. Recent work highlights the importance of genetic variants that influence brain structure and function in conferring risk for polygenic obesity. The neurotransmitter dopamine (DA) has a pivotal role in energy balance by integrating metabolic signals with circuits supporting cognitive, perceptual, and appetitive functions that guide feeding. It has also been established that diet and obesity alter DA signaling, leading to compulsive-like feeding and neurocognitive impairments. This raises the possibility that genetic variants that influence DA signaling and adaptation confer risk for overeating and cognitive decline. Here, we consider the role of two common gene variants, FTO and TaqIA rs1800497 in driving gene × environment interactions promoting obesity, metabolic dysfunction, and cognitive change via their influence on DA receptor subtype 2 (DRD2) signaling. Recent work highlights the importance of genetic variants that influence brain structure and function in conferring risk for polygenic obesity. The neurotransmitter dopamine (DA) has a pivotal role in energy balance by integrating metabolic signals with circuits supporting cognitive, perceptual, and appetitive functions that guide feeding. It has also been established that diet and obesity alter DA signaling, leading to compulsive-like feeding and neurocognitive impairments. This raises the possibility that genetic variants that influence DA signaling and adaptation confer risk for overeating and cognitive decline. Here, we consider the role of two common gene variants, FTO and TaqIA rs1800497 in driving gene × environment interactions promoting obesity, metabolic dysfunction, and cognitive change via their influence on DA receptor subtype 2 (DRD2) signaling. a molecule that binds to, and activates, a receptor. alternative forms of the same gene. a type of cell in the central nervous system that was traditionally believed to perform support and maintenance for neurons, but is now believed to have a more active role in cell signaling and computation. the cognitive phenomenon where the relative value of a reward decreases as the delay in receiving it increases. a type of signaling molecule that regulates the function of other cells. heritable behavioral and/or neurocognitive traits that are associated with, or convey risk for, a syndrome. a form of interaction between genes, where the presence of a certain allele for one gene modifies or masks the expression of a different gene. a computer-based data mining-based method for determining proteome-wide protein-protein interactions (PPIs). This method is based on the ability of a program to predict, based on the literature and known sequence of the protein, the possible physical interaction between proteins. This method is typically used to narrow down potential partners involved in a signaling cascade. a series of cellular events that are triggered by an immune reaction and that result in pathological inflammation. the tendency of certain alleles of different genes to be inherited together at a rate greater than chance. a class of hydrophobic organic molecules that encompasses fats and oils. a protein complex that acts as a master transcriptional regulator in the cellular response to various stimuli, including nutrients. It is fundamental for the control of immune responses and regulates cell survival/death, cytokine production, and response to free radical damage. It also mediates the inflammatory response to nutrient overload in the brain [122,142–144] and directly controls DRD2 expression [145]. type of inheritance where the contributions of multiple genes determine a single characteristic. a variation in a genetic location of interest that can be revealed by the digestion of the gene with restriction enzymes. Different gene variations are reflected by different lengths of the DNA fragments after digestion. a variation in a single nucleotide at a specific position in the genome. a family of membrane receptors that recognize structures such as microbes and mediate immune responses. In the central nervous system, TLR are expressed on neurons and glia and mediate diet-induced inflammation through various mechanism, including direct binding of fatty acids [148–151].