Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Integrative Biology

The obese brain as a heritable phenotype: a combined morphometry and twin study

International Journal of Obesity volume 41, pages 458–466 (2017)Cite this article

Subjects

Abstract

Background:

Body weight and adiposity are heritable traits. To date, it remains unknown whether obesity-associated brain structural alterations are under a similar level of genetic control.

Methods:

For this study, we utilized magnetic resonance imaging data from the Human Connectome Project. Voxel-based morphometry was used to investigate associations between body mass index (BMI) and regional gray matter volume (GMV) in a sample of 875 young adults with a wide BMI range (386 males/489 females; age 28.8±3.7 years; BMI 26.6±5.3 kg m−2) that included 86 pairs of monozygotic twins and 82 pairs of dizygotic twins. Twin data were analyzed by applying the additive genetic, common environmental and residual effects model to determine heritability of brain regions that were associated with BMI.

Results:

We observed positive associations between BMI and GMV in the ventromedial prefrontal cortex and the right cerebellum and widespread negative associations within the prefrontal cortex, cerebellum, temporal lobes and distinct subcortical structures. Varying degrees of heritability were found for BMI-associated brain regions, with the highest heritability estimates for cerebellar GMV and subcortical structures.

Conclusions:

These data indicate that brain regions associated with obesity are subject to differing levels of genetic control and environmental influences. Specific brain regions with high heritability might represent an inherent vulnerability factor for obesity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Ogden CL, Carroll MD, Kit BK, Flegal KM . Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA 2014; 311: 806–814.

    Article  CAS  Google Scholar 

  2. Berridge KC, Ho C-Y, Richard JM, DiFeliceantonio AG . The tempted brain eats: pleasure and desire circuits in obesity and eating disorders. Brain Res 2010; 1350: 43–64.

    Article  CAS  Google Scholar 

  3. Kenny PJ . Reward mechanisms in obesity: new insights and future directions. Neuron 2011; 69: 664–679.

    Article  CAS  Google Scholar 

  4. Volkow ND, Wang G-J, Tomasi D, Baler RD . Obesity and addiction: neurobiological overlaps. Obes Rev 2013; 14: 2–18.

    Article  CAS  Google Scholar 

  5. Horstmann A, Busse FP, Mathar D, Muller K, Lepsien J, Schlogl H et al. Obesity-related differences between women and men in brain structure and goal-directed behavior. Front Hum Neurosci 2011; 5: 58.

    Article  Google Scholar 

  6. Janowitz D, Wittfeld K, Terock J, Freyberger HJ, Hegenscheid K, Völzke H et al. Association between waist circumference and gray matter volume in 2344 individuals from two adult community-based samples. Neuroimage 2015; 122: 149–157.

    Article  Google Scholar 

  7. Kurth F, Levitt JG, Phillips OR, Luders E, Woods RP, Mazziotta JC et al. Relationships between gray matter, body mass index, and waist circumference in healthy adults. Hum Brain Mapp 2013; 34: 1737–1746.

    Article  Google Scholar 

  8. Masouleh SK, Arélin K, Horstmann A, Lampe L, Kipping JA, Luck T et al. Higher body mass index in older adults is associated with lower gray matter volume: implications for memory performance. Neurobiol Aging 2016; 40: 1–10.

    Article  Google Scholar 

  9. Pannacciulli N, Del Parigi A, Chen K, Le DSNT, Reiman EM, Tataranni PA . Brain abnormalities in human obesity: a voxel-based morphometric study. Neuroimage 2006; 31: 1419–1425.

    Article  Google Scholar 

  10. Taki Y, Kinomura S, Sato K, Inoue K, Goto R, Okada K et al. Relationship between body mass index and gray matter volume in 1,428 healthy individuals. Obesity 2008; 16: 119–124.

    Article  Google Scholar 

  11. Walther K, Birdsill AC, Glisky EL, Ryan L . Structural brain differences and cognitive functioning related to body mass index in older females. Hum Brain Mapp 2010; 31: 1052–1064.

    Article  Google Scholar 

  12. Brooks SJ, Cedernaes J, Schiöth HB . Increased prefrontal and parahippocampal activation with reduced dorsolateral prefrontal and insular cortex activation to food images in obesity: a meta-analysis of fMRI studies. PLoS One 2013; 8: e60393.

    Article  CAS  Google Scholar 

  13. Smucny J, Cornier M-A, Eichman LC, Thomas EA, Bechtell JL, Tregellas JR . Brain structure predicts risk for obesity. Appetite 2012; 59: 859–865.

    Article  Google Scholar 

  14. Yokum S, Ng J, Stice E . Relation of regional gray and white matter volumes to current BMI and future increases in BMI: a prospective MRI study. Int J Obes 2012; 36: 656–664.

    Article  CAS  Google Scholar 

  15. Elks CE, den Hoed M, Zhao JH, Sharp SJ, Wareham NJ, Loos RJF et al. Variability in the heritability of body mass index: a systematic review and meta-regression. Front Endocrinol 2012; 3: 29.

    Article  Google Scholar 

  16. Hinney A, Vogel CIG, Hebebrand J . From monogenic to polygenic obesity: recent advances. Eur Child Adolesc Psychiatry 2010; 19: 297–310.

    Article  Google Scholar 

  17. Loos RJF, Bouchard C . FTO: the first gene contributing to common forms of human obesity. Obes Rev 2008; 9: 246–250.

    Article  CAS  Google Scholar 

  18. Stice E, Spoor S, Bohon C, Small DM . Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele. Science 2008; 322: 449–452.

    Article  CAS  Google Scholar 

  19. Ziauddeen H, Farooqi IS, Fletcher PC . Obesity and the brain: how convincing is the addiction model? Nat Rev Neurosci 2012; 13: 279–286.

    Article  CAS  Google Scholar 

  20. Toga AW, Thompson PM . Genetics of brain structure and intelligence. Annu Rev Neurosci 2005; 28: 1–23.

    Article  CAS  Google Scholar 

  21. Van Essen DC, Smith SM, Barch DM, Behrens TEJ, Yacoub E, Ugurbil K . The WU-Minn Human Connectome Project: an overview. Neuroimage 2013; 80: 62–79.

    Article  Google Scholar 

  22. Van Essen DC, Ugurbil K, Auerbach E, Barch D, Behrens TEJ, Bucholz R et al. The Human Connectome Project: a data acquisition perspective. Neuroimage 2012; 62: 2222–2231.

    Article  CAS  Google Scholar 

  23. Ashburner J, Friston KJ . Voxel-based morphometry–the methods. Neuroimage 2000; 11: 805–821.

    Article  CAS  Google Scholar 

  24. Kringelbach ML . The human orbitofrontal cortex: linking reward to hedonic experience. Nat Rev Neurosci 2005; 6: 691–702.

    Article  CAS  Google Scholar 

  25. Weise CM, Thiyyagura P, Reiman EM, Chen K, Krakoff J . Fat-free body mass but not fat mass is associated with reduced gray matter volume of cortical brain regions implicated in autonomic and homeostatic regulation. Neuroimage 2013; 64: 712–721.

    Article  Google Scholar 

  26. Zhu J-N, Wang J-J . The cerebellum in feeding control: possible function and mechanism. Cell Mol Neurobiol 2007; 28: 469–478.

    Article  Google Scholar 

  27. Veit R, Kullmann S, Heni M, Machann J, Häring H-U, Fritsche A et al. Reduced cortical thickness associated with visceral fat and BMI. Neuroimage Clin 2014; 6: 307–311.

    Article  Google Scholar 

  28. Frank S, Kullmann S, Veit R . Food related processes in the insular cortex. Front Hum Neurosci 2013; 7: 499.

    Article  Google Scholar 

  29. Weston CSE . Another major function of the anterior cingulate cortex: the representation of requirements. Neurosci Biobehav Rev 2012; 36: 90–110.

    Article  CAS  Google Scholar 

  30. Mueller SG, Laxer KD, Cashdollar N, Buckley S, Paul C, Weiner MW . Voxel-based optimized morphometry (VBM) of gray and white matter in temporal lobe epilepsy (TLE) with and without mesial temporal sclerosis. Epilepsia 2006; 47: 900–907.

    Article  Google Scholar 

  31. Wang GJ, Volkow ND, Logan J, Pappas NR, Wong CT, Zhu W et al. Brain dopamine and obesity. Lancet 2001; 357: 354–357.

    Article  CAS  Google Scholar 

  32. Weise CM, Thiyyagura P, Reiman EM, Chen K, Krakoff J . A potential role for the midbrain in integrating fat-free mass determined energy needs: an H2 (15) O PET study. Hum Brain Mapp 2015; 36: 2406–2415.

    Article  Google Scholar 

  33. Siep N, Roefs A, Roebroeck A, Havermans R, Bonte ML, Jansen A . Hunger is the best spice: an fMRI study of the effects of attention, hunger and calorie content on food reward processing in the amygdala and orbitofrontal cortex. Behav Brain Res 2009; 198: 149–158.

    Article  Google Scholar 

  34. Rijsdijk FV, Viding E, De Brito S, Forgiarini M, Mechelli A et al. Heritable variations in gray matter concentration as a potential endophenotype for psychopathic traits. Arch Gen Psychiatry 2010; 67: 406–413.

    Article  Google Scholar 

  35. Feng R, Zhou G, Zhang M, Zhang H . Analysis of twin data using SAS. Biometrics 2009; 65: 584–589.

    Article  Google Scholar 

  36. White T, Andreasen NC, Nopoulos P . Brain volumes and surface morphology in monozygotic twins. Cereb Cortex 2002; 12: 486–493.

    Article  Google Scholar 

  37. Thompson PM, Cannon TD, Narr KL, van Erp T, Poutanen V-P, Huttunen M et al. Genetic influences on brain structure. Nat Neurosci 2001; 4: 1253–1258.

    Article  CAS  Google Scholar 

  38. Raschpichler M, Straatman K, Schroeter ML, Arelin K, Schlögl H, Fritzsch D et al. Abdominal fat distribution and its relationship to brain changes: the differential effects of age on cerebellar structure and function: a cross-sectional, exploratory study. BMJ Open 2013; 3, pii e001915.

    Article  Google Scholar 

  39. Dimitropoulos A, Tkach J, Ho A, Kennedy J . Greater corticolimbic activation to high-calorie food cues after eating in obese vs. normal-weight adults. Appetite 2012; 58: 303–312.

    Article  Google Scholar 

  40. Gearhardt AN, Yokum S, Stice E, Harris JL, Brownell KD . Relation of obesity to neural activation in response to food commercials. Soc Cogn Affect Neurosci 2014; 9: 932–938.

    Article  Google Scholar 

  41. Tomasi D, Wang G-J, Wang R, Backus W, Geliebter A, Telang F et al. Association of body mass and brain activation during gastric distention: implications for obesity. PLoS One 2009; 4: e6847.

    Article  Google Scholar 

  42. Tuulari JJ, Karlsson HK, Hirvonen J, Salminen P, Nuutila P, Nummenmaa L . Neural circuits for cognitive appetite control in healthy and obese individuals: an fMRI study. PLoS One 2015; 10: e0116640.

    Article  Google Scholar 

  43. Buckner RL . The cerebellum and cognitive function: 25 years of insight from anatomy and neuroimaging. Neuron 2013; 80: 807–815.

    Article  CAS  Google Scholar 

  44. Strick PL, Dum RP, Fiez JA . Cerebellum and nonmotor function. Annu Rev Neurosci 2009; 32: 413–434.

    Article  CAS  Google Scholar 

  45. Burger KS, Stice E . Greater striatopallidal adaptive coding during cue–reward learning and food reward habituation predict future weight gain. Neuroimage 2014; 99: 122–128.

    Article  Google Scholar 

  46. Small DM . Individual differences in the neurophysiology of reward and the obesity epidemic. Int J Obes 2009; 33: S44–S48.

    Article  Google Scholar 

  47. Mueller K, Möller HE, Horstmann A, Busse F, Lepsien J, Blüher M et al. Physical exercise in overweight to obese individuals induces metabolic- and neurotrophic-related structural brain plasticity. Front Hum Neurosci 2015; 9: 372.

    Article  Google Scholar 

  48. Prehn K, Jumpertz von Schwartzenberg R, Mai K, Zeitz U, Witte AV, Hampel D et al. Caloric restriction in older adults-differential effects of weight loss and reduced weight on brain structure and function. Cereb Cortex 2016. e-pub ahead of print 1 February 2016 pii bhw008.

  49. Tuulari JJ . Effects of obesity and weight loss following bariatric surgery on brain function structural integrity and metabolism, 2015. Available at www.doria.fi.

Download references

Acknowledgements

Data were provided (in part) by the Human Connectome Project, WU-Minn Consortium (Principal Investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centers that support the NIH Blueprint for Neuroscience Research and by the McDonnell Center for Systems Neuroscience at Washington University. This study was supported by the IFB AdiposityDiseases, Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01E01001 (http://www.bmbf.de) and the German Research Foundation (DFG; http://www.dfg.de), within the framework of the CRC 1052 Obesity Mechanisms to Project A6 (to BP).

Author information

Authors and Affiliations

  1. Department of Neurology, University of Leipzig, Leipzig, Germany

    C M Weise

  2. Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, AZ, USA

    P Piaggi & J Krakoff

  3. Department of Diagnostic and Interventional Radiology, University of Leipzig, Leipzig, Germany

    M Reinhardt

  4. Banner Alzheimer’s Institute, Phoenix, AZ, USA

    K Chen & C R Savage

  5. Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany

    B Pleger

  6. Department of Neurology, BG University Clinic Bergmannsheil, Ruhr-University Bochum, Bochum, Germany

    B Pleger

Authors
  1. C M Weise
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P Piaggi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Reinhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C R Savage
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J Krakoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. B Pleger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C M Weise.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on International Journal of Obesity website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Weise, C., Piaggi, P., Reinhardt, M. et al. The obese brain as a heritable phenotype: a combined morphometry and twin study. Int J Obes 41, 458–466 (2017). https://doi.org/10.1038/ijo.2016.222

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2016.222

This article is cited by

Search

Advanced search

Quick links