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Genetic risk for obesity predicts nucleus accumbens size and responsivity to real-world food cues.

ABSTRACT: Obesity is a major public health concern that involves an interaction between genetic susceptibility and exposure to environmental cues (e.g., food marketing); however, the mechanisms that link these factors and contribute to unhealthy eating are unclear. Using a well-known obesity risk polymorphism (FTO rs9939609) in a sample of 78 children (ages 9-12 y), we observed that children at risk for obesity exhibited stronger responses to food commercials in the nucleus accumbens (NAcc) than children not at risk. Similarly, children at a higher genetic risk for obesity demonstrated larger NAcc volumes. Although a recessive model of this polymorphism best predicted body mass and adiposity, a dominant model was most predictive of NAcc size and responsivity to food cues. These findings suggest that children genetically at risk for obesity are predisposed to represent reward signals more strongly, which, in turn, may contribute to unhealthy eating behaviors later in life.

SUBMITTER: Rapuano KM

PROVIDER: S-EPMC5224374 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Genetic risk for obesity predicts nucleus accumbens size and responsivity to real-world food cues.

Rapuano Kristina M KM Zieselman Amanda L AL Kelley William M WM Sargent James D JD Heatherton Todd F TF Gilbert-Diamond Diane D

Proceedings of the National Academy of Sciences of the United States of America 20161219 1

Obesity is a major public health concern that involves an interaction between genetic susceptibility and exposure to environmental cues (e.g., food marketing); however, the mechanisms that link these factors and contribute to unhealthy eating are unclear. Using a well-known obesity risk polymorphism (FTO rs9939609) in a sample of 78 children (ages 9-12 y), we observed that children at risk for obesity exhibited stronger responses to food commercials in the nucleus accumbens (NAcc) than children ...[more]

PMID: 27994159

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Project description:ImportanceSchizophrenia is associated with a reduced life expectancy of 15 to 20 years owing to a high prevalence of cardiometabolic disorders. Obesity, a key risk factor for the development of cardiometabolic alterations, is more prevalent in individuals with schizophrenia. Although obesity is linked to the altered reward processing of food cues, no studies have investigated this link in schizophrenia without the confounds of antipsychotics and illness chronicity.ObjectiveTo investigate neural responsivity to food cues in first-episode psychosis without the confounds of antipsychotic medication or illness chronicity.Design, setting, and participantsA case-control study was conducted from January 31, 2015, to September 30, 2018, in London, United Kingdom, of 29 patients with first-episode psychosis who were not taking antipsychotic medication and 28 matched controls.Main outcomes and measuresParticipants completed a food cue paradigm while undergoing a functional magnetic resonance imaging scan. Neural activation was indexed using the blood oxygen level-dependent hemodynamic response. The Dietary Instrument for Nutrition Education was used to measure diet, and the International Physical Activity Questionnaire was used to measure exercise.ResultsThere were no significant differences in age, sex, or body mass index between the 29 patients (25 men and 4 women; mean [SD] age, 26.1 [4.8] years) and 28 controls (22 men and 6 women; mean [SD] age, 26.4 [5.5] years). Relative to controls, patients consumed more saturated fat (t46 = -3.046; P = .004) and undertook less high-intensity (U = 304.0; P = .01) and low-intensity (U = 299.5; P = .005) weekly exercise. There were no group differences in neural responses to food vs nonfood cues in whole-brain or region-of-interest analyses of the nucleus accumbens, insula, or hypothalamus. Body mass index was inversely correlated with the mean blood oxygen level-dependent signal in the nucleus accumbens in response to food vs nonfood cues in controls (R = -0.499; P = .01) but not patients (R = 0.082; P = .70).Conclusions and relevanceRelative to controls, patients with first-episode psychosis who were not taking antipsychotic medication consumed more saturated fat and showed an altered association between body mass index and neural response to food cues in the absence of differences in neural responses to food cues. These findings highlight how maladaptive eating patterns and alterations in the association between body mass index and neural responses to food cues are established early in the course of schizophrenia.

Project description:Obesity is one of the leading health concerns in the United States. Studies from human and rodent models suggest that inherent differences in the function of brain motivation centers, including the nucleus accumbens (NAc), contribute to overeating and thus obesity. For example, there are basal enhancements in the excitability of NAc GABAergic medium spiny neurons (MSN) and reductions in basal expression of AMPA-type glutamate receptors in obesity-prone vs obesity-resistant rats. However, very little is known about the regulation of extracellular glutamate and GABA within the NAc of these models. Here we gave obesity-prone and obesity-resistant rats stable isotope-labeled glucose (13 C6 -glucose) and used liquid chromatography mass spectrometry (LC-MS) analysis of NAc dialysate to examine the real-time incorporation of 13 C6 -glucose into glutamate, glutamine, and GABA. This novel approach allowed us to identify differences in glucose utilization for neurotransmitter production between these selectively bred lines. We found that voluntarily ingested or gastrically infused 13 C6 -glucose rapidly enters the NAc and is incorporated into 13 C2 -glutamine, 13 C2 -glutamate, and 13 C2 -GABA in both groups within minutes. However, the magnitude of increases in NAc 13 C2 -glutamine and 13 C2 -GABA were lower in obesity-prone than in obesity-resistant rats, while basal levels of glutamate were elevated. This suggested that there may be differences in the astrocytic regulation of these analytes. Thus, we next examined NAc glutamine synthetase, GAD67, and GLT-1 protein expression. Consistent with reduced 13 C2 -glutamine and 13 C2 -GABA, NAc glutamine synthetase and GLT-1 protein expression were reduced in obesity-prone vs obesity-resistant groups. Taken together, these data show that NAc glucose utilization differs dramatically between obesity-prone and obesity-resistant rats, favoring glutamate over GABA production in obesity-prone rats and that reductions in NAc astrocytic recycling of glutamate contribute to these differences. These data are discussed in light of established differences in NAc function between these models and the role of the NAc in feeding behavior.

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Genetic risk for obesity predicts nucleus accumbens size and responsivity to real-world food cues.

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Genetic risk for obesity predicts nucleus accumbens size and responsivity to real-world food cues.

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