Relation Between Obesity and Blunted Striatal Response to Food Is Moderated by TaqIA A1 Allele

Oregon Research Institute, 1715 Franklin Boulevard, Eugene, OR 97403, USA. .
Science (Impact Factor: 33.61). 11/2008; 322(5900):449-52. DOI: 10.1126/science.1161550
Source: PubMed


The dorsal striatum plays a role in consummatory food reward, and striatal dopamine receptors are reduced in obese individuals, relative to lean individuals, which suggests that the striatum and dopaminergic signaling in the striatum may contribute to the development of obesity. Thus, we tested whether striatal activation in response to food intake is related to current and future increases in body mass and whether these relations are moderated by the presence of the A1 allele of the TaqIA restriction fragment length polymorphism, which is associated with dopamine D2 receptor (DRD2) gene binding in the striatum and compromised striatal dopamine signaling. Cross-sectional and prospective data from two functional magnetic resonance imaging studies support these hypotheses, which implies that individuals may overeat to compensate for a hypofunctioning dorsal striatum, particularly those with genetic polymorphisms thought to attenuate dopamine signaling in this region.

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Available from: Cara Bohon
    • "Impulsivity and altered dopamine transmission are also observed in obesity and BED (Dawe & Loxton, 2004; Stice et al., 2008; Wang et al., 2011; Michaelides et al., 2012; Babbs et al., 2013; Schag et al., 2013) contributing to a widespread view that palatable energy-dense foods might be " addictive " . Although a hotly debated issue (Salamone & Correa, 2013; Smith & Robbins, 2013; Ziauddeen & Fletcher, 2013), there is some consensus for the existence of " addiction-like eating behavior " as exemplified by binge-eating (Davis, 2013; Smith & Robbins, 2013; Ziauddeen & Fletcher, 2013; Hebebrand et al., 2014). "
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    ABSTRACT: High impulsivity, mediated through ventral striatal dopamine signaling, represents an established risk factor for substance abuse and may likewise confer vulnerability to pathological overeating. Mechanistically, the assumption is that trait impulsivity facilitates the initiation of maladaptive eating styles or choices. However, whether consumption of appetitive macronutrients themselves causes deficits in impulse control and striatal signaling, thereby contributing to cognitive changes permissive of overeating behavior, has yet to be considered. We examined the effects of chronic maintenance on restricted equicaloric, yet high-fat or high-sugar, diets (48 kcal/day; 60 kcal% fat or sucrose) on rats' performance in the 5-choice serial reaction time task (5CSRTT) indexing impulsivity and attention. Markers of dopamine signaling in the dorsal and ventral striatum, and plasma insulin and leptin levels, were also assessed. Rats maintained on the high-fat diet (HFD) were more impulsive, while the high-sugar diet (HSD) did not alter task performance. Importantly, body weight and hormone levels were similar between groups when behavioral changes were observed. Maintenance on HFD, but not HSD, reduced levels of dopamine D2 receptor (D2 R), cAMP response element-binding protein (CREB) and phospho-CREB (Ser133) proteins in the ventral, but not dorsal, striatum. D2 R expression in the ventral striatum also negatively correlated with impulsive responding independent of diet. These data indicate that chronic exposure to even limited amounts of high-fat foods may weaken impulse control and alter neural signaling in a manner associated with vulnerability to addictions-findings that have serious implications for the propagation of uncontrolled eating behavior in obesity and binge-eating disorder. This article is protected by copyright. All rights reserved.
    No preview · Article · Nov 2015 · European Journal of Neuroscience
    • "The mechanism of striatal dopaminergic hypofunctioning, as found in reduced striatal D2-receptor availability, ie, blunted striatal response to food, is believed to be a major contributor to overeating according to the reward-deficiency model of obesity (Blum et al, 2014; Wang et al, 2001). In addition, a blunted striatal response in obesity appears to be moderated by a Taq1A polymorphism that influences the dopamine D2-receptor binding (Stice et al, 2008). However, a causal interpretation of such findings has led to some controversy (Berridge, 2009). "
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    ABSTRACT: Reward sensitivity and possible alterations in the dopaminergic reward system are associated with obesity. We therefore aimed to investigate the influence of dopamine depletion on food reward processing. We investigated 34 female subjects in a randomized placebo-controlled, within-subject design (BMI=27.0 kg/m(2)±4.79 SD; age=28y±4.97 SD) using an acute phenylalanine/tyrosine depletion drink representing dopamine depletion and a balanced amino acid drink as the control condition. Brain activity was measured with functional magnetic resonance imaging during a 'wanting' and 'liking' rating of food items. Eating behavior-related traits and states were assessed on the basis of questionnaires. Dopamine depletion resulted in reduced activation in the striatum and higher activation in the superior frontal gyrus independent of body mass index (BMI). Brain activity during the wanting task activated a more distributed network than during the liking task. This network included gustatory, memory, visual, reward and frontal regions. An interaction effect of dopamine depletion and the wanting/liking task was observed in the hippocampus. The interaction with the covariate BMI was significant in motor and control regions but not in the striatum. Our results support the notion of altered brain activity in the reward and prefrontal network with blunted dopaminergic action during food reward processing. This effect is, however, independent of BMI, which contradicts the reward deficiency hypothesis. This hints to hypothesis suggesting a different or more complex mechanism underlying the dopaminergic reward function in obesity.Neuropsychopharmacology accepted article preview online, 09 October 2015. doi:10.1038/npp.2015.313.
    No preview · Article · Oct 2015 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
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    • "Thus, the current data are consistent with recent work showing that obesity susceptible rats are hyper-responsive to the motivational properties of food cues prior to the development of obesity, and support the idea that basal differences in striatal function may contribute to the development obesity in susceptible populations [47]. Interestingly, fMRI studies in people find that while striatal activation in response to food cues is enhanced in susceptible individuals prior to the development of obesity [7,12,17,57–60], striatal activations in response to the consumption of food itself is reduced after obesity develops [11] [56]. These data suggest that responsivity of striatal systems may be dynamically and differentially influenced by food cues versus food consumption. "
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    ABSTRACT: Obesity is a significant problem in the United States, with roughly one third of adults having a body mass index (BMI) over thirty. Recent evidence from human studies suggests that pre-existing differences in the function of mesolimbic circuits that mediate motivational processes may promote obesity and hamper weight loss. However, few preclinical studies have examined pre-existing neurobehavioral differences related to the function of mesolimbic systems in models of individual susceptibility to obesity. Here, we used selectively bred obesity-prone and obesity-resistant rats to examine 1) the effect of a novel "junk-food" diet on the development of obesity and metabolic dysfunction, 2) over-consumption of "junk-food" in a free access procedure, 3) motivation for food using instrumental procedures, and 4) cocaine-induced locomotor activity as an index of general mesolimbic function. As expected, eating a sugary, fatty, "junk-food" diet exacerbated weight gain and increased fasted insulin levels only in obesity-prone rats. In addition, obesity-prone rats continued to over-consume junk-food during discrete access testing, even when this same food was freely available in the home cage. Furthermore, when asked to press a lever to obtain food in an instrumental task, rates of responding were enhanced in obesity-prone versus obesity-resistant rats. Finally, obesity-prone rats showed a stronger locomotor response to 15mg/kg cocaine compared to obesity-resistant rats prior to any diet manipulation. This enhanced sensitivity to this dose of cocaine is indicative of basal differences in the function of mesolimbic circuits in obesity-prone rats. We speculate that pre-existing differences in motivational systems may contribute to over-consumption and enhanced motivation in susceptible individuals.
    Full-text · Article · Oct 2015 · Physiology & Behavior
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