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Research Article

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

Kristina M. Rapuano, Amanda L. Zieselman, William M. Kelley, James D. Sargent, Todd F. Heatherton, and View ORCID ProfileDiane Gilbert-Diamond
PNAS January 3, 2017 114 (1) 160-165; first published December 19, 2016 https://doi.org/10.1073/pnas.1605548113
Kristina M. Rapuano
aPsychological and Brain Sciences Department, Dartmouth College, Hanover, NH 03755;
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  • For correspondence: Kristina.M.Rapuano.GR@Dartmouth.edu
Amanda L. Zieselman
aPsychological and Brain Sciences Department, Dartmouth College, Hanover, NH 03755;
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William M. Kelley
aPsychological and Brain Sciences Department, Dartmouth College, Hanover, NH 03755;
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James D. Sargent
bNorris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756;cDepartment of Pediatrics, Geisel School of Medicine at Dartmouth, Hanover, NH 03755;
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Todd F. Heatherton
aPsychological and Brain Sciences Department, Dartmouth College, Hanover, NH 03755;bNorris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756;
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Diane Gilbert-Diamond
bNorris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756;dDepartment of Epidemiology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755
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  • ORCID record for Diane Gilbert-Diamond
  1. Edited by Ahmad R. Hariri, Duke University, Durham, NC, and accepted by Editorial Board Member Leslie G. Ungerleider November 3, 2016 (received for review April 5, 2016)

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Significance

Genetic predisposition and sensitivity to environmental cues jointly give rise to maladaptive human behaviors, such as unhealthy eating. Despite the dramatic rise in obesity rates, the relationship between these factors is not well understood. Here we show that children genetically at risk for obesity exhibit stronger reward-related responses to real-world food cues (i.e., food advertisements) in the nucleus accumbens, a brain area canonically associated with reward processing. Additionally, this structure is larger in children at a higher risk for obesity. Taken together, these findings offer one explanation for how genetic risk for obesity may predispose individuals to engage in unhealthy eating behaviors and may inform strategies targeting early intervention.

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.

  • reward
  • obesity
  • fMRI
  • brain morphometry
  • genetic risk

Footnotes

  • ↵1To whom correspondence should be addressed. Email: Kristina.M.Rapuano.GR{at}Dartmouth.edu.
  • Author contributions: K.M.R., A.L.Z., W.M.K., J.D.S., T.F.H., and D.G.-D. designed research; K.M.R. and A.L.Z. performed research; D.G.-D. contributed new reagents/analytic tools; K.M.R., A.L.Z., and W.M.K. analyzed data; and K.M.R. and W.M.K. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission. A.R.H. is a Guest Editor invited by the Editorial Board.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1605548113/-/DCSupplemental.

Freely available online through the PNAS open access option.

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Genetic risk for obesity predicts response to food
Kristina M. Rapuano, Amanda L. Zieselman, William M. Kelley, James D. Sargent, Todd F. Heatherton, Diane Gilbert-Diamond
Proceedings of the National Academy of Sciences Jan 2017, 114 (1) 160-165; DOI: 10.1073/pnas.1605548113

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Genetic risk for obesity predicts response to food
Kristina M. Rapuano, Amanda L. Zieselman, William M. Kelley, James D. Sargent, Todd F. Heatherton, Diane Gilbert-Diamond
Proceedings of the National Academy of Sciences Jan 2017, 114 (1) 160-165; DOI: 10.1073/pnas.1605548113
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