Neural vulnerability factors for obesity

Abstract

Multiple theories identify neural vulnerability factors that may increase risk for overeating and weight gain. Early cross-sectional neuroimaging studies were unable to determine whether aberrant neural responsivity was a risk factor for or a consequence of overeating. More recent obesity risk, prospective, repeated-measures, and experimental neuroimaging studies with humans have advanced knowledge of etiologic processes and neural plasticity resulting from overeating. Herein, we review evidence from these more rigorous human neuroimaging studies, in conjunction with behavioral measures reflecting neural function, as well as experiments with animals that investigated neural vulnerability theories for overeating. Findings provide support for the reward surfeit theory that posits that individuals at risk for obesity initially show hyper-responsivity of reward circuitry to high-calorie food tastes, which theoretically drives elevated intake of such foods. However, findings provide little support for the reward deficit theory that postulates that individuals at risk for obesity show an initial hypo-responsivity of reward circuitry that motives overeating. Further, results provide support for the incentive sensitization and dynamic vulnerability theories that propose that overconsumption of high-calorie foods results in increased reward and attention region responsivity to cues that are associated with hedonic reward from intake of these high-calorie foods via conditioning, as well as a simultaneous decrease in reward region responsivity to high-calorie food tastes. However, there is little evidence that this induced reduction in reward region response to high-calorie food tastes drives an escalation in overeating. Finally, results provide support for the theory that an initial deficit in inhibitory control and a bias for immediate reward contribute to overconsumption of high-calorie foods. Findings imply that interventions that reduce reward and attention region responsivity to food cues and increase inhibitory control should reduce overeating and excessive weight gain, an intervention theory that is receiving support in randomized trials.

Keywords: Obesity; Prospective; Reward circuitry; Weight gain; fMRI.

Conflict of interest statement

Conflicts

Neither author reports any conflict of interest in relation to the literature reviewed in this manuscript.

Copyright © 2018 Elsevier Ltd. All rights reserved.

Figures

Figure 1.

Integrative signaling of homeostatic and hedonic feeding in the CNS. Major monosynaptic connections are shown, emphasizing the extensive anatomical interconnectivity of functional sets of circuitry that mediate aspects of feeding. Teal-framed boxes represent medial hypothalamic sites (PVN, ARC) that had historically been considered key sites for energy homeostasis, coordinating the regulation of body weight, metabolism, and short- and long-term feeding. Purple-framed boxes represent the central dopaminergic cell bodies (VTA/SNC) and mesolimbic projections (striatum/NAcc), historically considered the major regulatory sites of motivated behaviors. The dopaminergic circuitry is connected with hypothalamic circuitry as well as limbic circuitry (amygdala/hippocampus/cortical areas). All regions shaded in pale blue represent CNS sites that are direct receptive targets of the endocrine signals of caloric abundance (insulin, leptin) and caloric need (ghrelin). These include brainstem (PBN/NTS: key relay nuclei for sensory and motor aspects of feeding); hypothalamic, dopaminergic, and limbic regions. Brain regions highlighted with magenta labelling are direct target regions for mu opioid stimulation of feeding. Cortex areas are a major focus of current animal and clinical studies and contributing sub-regions differ between rodents and humans; however the OFC and subareas of the PFC are implicated for both. ARC, arcuate nucleus; PVN, paraventricular nucleus of the hypothalamus; LH, lateral hypothalamic area; NAcc, nucleus accumbens; VTA, ventral tegmental area; SNC, substantia nigra pars compacta; NTS, nucleus of the tractus solitarius; PBN, parabrachial nucleus; dlPFC, dorsolateral prefrontal cortex; vlPFC, ventrolateral prefrontal cortex; vmPFC, ventromedial prefrontal cortex; PPTN, pedunculopontine tegmental nucleus; OFC, orbitofrontal cortex. Reproduced with permission from Stice et al., 2013.

Figure 2.

Presentation of a refined version of the Dynamic Vulnerability Model of Obesity