Association between olfactory receptor genes, eating behavior traits and adiposity: Results from the Quebec Family Study

Department of Social and Preventive Medicine, Laval University, Quebec, Canada.
Physiology & Behavior (Impact Factor: 2.98). 10/2011; 105(3):772-6. DOI: 10.1016/j.physbeh.2011.10.015
Source: PubMed


Obesity is a major health problem that can be influenced by eating behaviors. Evidence suggests that the sensory properties of food influence eating behaviors and lead to overeating and overweight. A previous genome-wide linkage scan for eating behavior traits assessed with the Three-Factor Eating Questionnaire (cognitive dietary restraint, disinhibition and hunger) performed in the Quebec Family Study (QFS) revealed a quantitative trait locus for disinhibition on chromosome 19p13. This region encodes a cluster of seven olfactory receptor (OR) genes, including OR7D4, previously associated with odor perceptions. Direct sequencing of the OR7D4 gene revealed 16 sequence variants. Nine OR7D4 sequence variants with minor allele frequency (MAF)>1% as well as 100 SNPs spanning the cluster of OR genes on 19p13 were tested for association with age- and sex-adjusted eating behaviors as well as adiposity traits in 890 subjects. One OR7D4 sequence variant (rs2878329 G>A) showed evidence of association with reduced levels of adiposity (p=0.03), cognitive dietary restraint (p=0.05) and susceptibility to hunger (p=0.008). None of the OR7D4 SNPs was associated with disinhibition, but a SNP (rs2240927) in another OR gene (OR7E24) showed evidence of association (p=0.03). Another SNP in the OR7G3 gene (rs10414255) was also found to be associated with adiposity and eating behaviors. These results are the first to suggest that variations in human olfactory receptor genes can influence eating behaviors and adiposity. The associations reported in the present study should be interpreted with caution considering the number of tests performed and considered as potential new hypotheses about the effects OR polymorphisms on eating behaviors and obesity that need to be further explored in other populations.

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    • "In this regard, it's worth noting that six of the top ten genes downregulated in InsR-deficient Glut4 neurons encode olfactory receptors (Supplemental Table 1). The Quebec Family Study has found a genetic association between a cluster of olfactory receptors on human chromosome 19 and eating behavior [14]. Our data provide a potential lead on how olfacto-sensory cues might become integrated in energy balance and peripheral metabolism. "
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    ABSTRACT: Insulin signaling in the CNS modulates satiety and glucose metabolism, but insulin target neurons are poorly defined. We have previously shown that ablation of insulin receptors (InsR) in Glut4-expressing tissues results in systemic abnormalities of insulin action. We propose that Glut4 neurons constitute an insulin-sensitive neuronal subset. We determined their gene expression profiles using flow-sorted hypothalamic Glut4 neurons. Gene ontology analyses demonstrated that Glut4 neurons are enriched in olfacto-sensory receptors, M2 acetylcholine receptors, and pathways required for the acquisition of insulin sensitivity. Following genetic ablation of InsR, transcriptome profiling of Glut4 neurons demonstrated impairment of the insulin, peptide hormone, and cAMP signaling pathways, with a striking upregulation of anion homeostasis pathway. Accordingly, hypothalamic InsR-deficient Glut4 neurons showed reduced firing activity. The molecular signature of Glut4 neurons is consistent with a role for this neural population in the integration of olfacto-sensory cues with hormone signaling to regulate peripheral metabolism.
    Full-text · Article · Jul 2014 · Molecular Metabolism
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    • "Several other genes close or within the additional suggestively significant SNPs (Additional file 1: Table S1) have been already involved in obesity related biological mechanisms. Among this list it is worth mentioning: ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1) gene (SSC9; ALGA0109564, P=9.01E-07) whose altered function contributes to steatosis and obesity in mice [34] and a polymorphism in this gene has been associated with obesity risk in Japanese subjects [35]; galanin receptor 3 (GALR3) gene (SSC5; M1GA0007458, P=1.25E-06) that is upregulated in adipose tissues of mice fed a high fat diet [36], and whose function is to bind galanin, a neuropeptide that regulates food intake, neurogenesis, memory, and gut secretion; olfactory receptor genes (two genes on SSC9, OR52N2 and OR56A3) have been associated with eating behaviour and adiposity in humans [37]; Parkinson protein 2 (PARK2) gene on SSC1 (ALGA0108518, P=5.48E-06) that is regulated in a lipid-dependent manner and modulates systemic fat uptake via ubiquitin ligase-dependent effects [38]; phosphodiesterase 4B, cAMP-specific (PDE4B) on SSC6 (ALGA0109354, P=5.95E-06) that has been already shown to be associated with BFT in pigs as well as with obesity in humans [39]; vacuolar protein sorting 13 homolog B (yeast) (VPS13B) on SSC4 (ALGA0024658, P=3.00E-05) that causes Cohen syndrome, characterized by truncal obesity [40]; iroquois homeobox 3 (IRX3) gene on SSC6 (M1GA0008432, P=4.66E-05), that is involved in the stress response after fat loss [41] and could be linked to obesity and type 2 diabetes through its pancreatic function [42]. Interestingly the second closest gene to this latter SSC6 SNP was FTO, that is well known to affect human obesity (i.e. "
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    ABSTRACT: Carcass fatness is an important trait in most pig breeding programs. Following market requests, breeding plans for fresh pork consumption are usually designed to reduce carcass fat content and increase lean meat deposition. However, the Italian pig industry is mainly devoted to the production of Protected Designation of Origin dry cured hams: pigs are slaughtered at around 160 kg of live weight and the breeding goal aims at maintaining fat coverage, measured as backfat thickness to avoid excessive desiccation of the hams. This objective has shaped the genetic pool of Italian heavy pig breeds for a few decades. In this study we applied a selective genotyping approach within a population of ~ 12,000 performance tested Italian Large White pigs. Within this population, we selectively genotyped 304 pigs with extreme and divergent backfat thickness estimated breeding value by the Illumina PorcineSNP60 BeadChip and performed a genome wide association study to identify loci associated to this trait. We identified 4 single nucleotide polymorphisms with P≤5.0E-07 and additional 119 ones with 5.0E-07<P≤5.0E-05. These markers were located throughout all chromosomes. The largest numbers were found on porcine chromosomes 6 and 9 (n=15), 4 (n=13), and 7 (n=12) while the most significant marker was located on chromosome 18. Twenty-two single nucleotide polymorphisms were in intronic regions of genes already recognized by the Pre-Ensembl Sscrofa10.2 assembly. Gene Ontology analysis indicated an enrichment of Gene Ontology terms associated with nervous system development and regulation in concordance with results of large genome wide association studies for human obesity. Further investigations are needed to evaluate the effects of the identified single nucleotide polymorphisms associated with backfat thickness on other traits as a pre-requisite for practical applications in breeding programs. Reported results could improve our understanding of the biology of fat metabolism and deposition that could also be relevant for other mammalian species including humans, confirming the role of neuronal genes on obesity.
    Full-text · Article · Nov 2012 · BMC Genomics
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    • "A gene that codes for the mammalian olfactory receptor, OR7D4, links food odors to human hunger, dietary restraint, and adiposity (Choquette et al., 2012). OR7D4 exemplifies a direct link1 from human social odors to their perception (Keller, Zhuang, Chi, Vosshall, & Matsunami, 2007) and to unconscious affects2 on human behavior associated with human olfactory-visual integration (Zhou, Hou, Zhou, & Chen, 2011); human brain activation associated with sexual preferences (Savic, Heden-Blomqvist, & Berglund, 2009), human learned odor hedonics; and motor function (Boulkroune, Wang, March, Walker, & Jacob, 2007). "
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    ABSTRACT: Olfactory cues directly link the environment to gene expression. Two types of olfactory cues, food odors and social odors, alter genetically predisposed hormone-mediated activity in the mammalian brain. The honeybee is a model organism for understanding the epigenetic link from food odors and social odors to neural networks of the mammalian brain, which ultimately determine human behavior. Pertinent aspects that extend the honeybee model to human behavior include bottom-up followed by top-down gene, cell, tissue, organ, organ-system, and organism reciprocity; neurophysiological effects of food odors and of sexually dimorphic, species-specific social odors; a model of motor function required for social selection that precedes sexual selection; and hormonal effects that link current neuroscience to social science affects on the development of animal behavior. As the psychological influence of food odors and social orders is examined in detail, the socioaffective nature of olfactory cues on the biologically based development of sexual preferences across all species that sexually reproduce becomes clearer.
    Full-text · Article · Mar 2012
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