Elsevier

Neuroscience

Volume 162, Issue 4, 15 September 2009, Pages 924-932
Neuroscience

Behavioural Neuroscience
Research Paper
Early life exposure to a high fat diet promotes long-term changes in dietary preferences and central reward signaling

https://doi.org/10.1016/j.neuroscience.2009.05.029Get rights and content

Abstract

Overweight and obesity in the United States continues to grow at epidemic rates in large part due to the overconsumption of calorically-dense palatable foods. Identification of factors influencing long-term macronutrient preferences may elucidate points of prevention and behavioral modification. In our current study, we examined the adult macronutrient preferences of mice acutely exposed to a high fat diet during the third postnatal week. We hypothesized that the consumption of a high fat diet during early life would alter the programming of central pathways important in adult dietary preferences. As adults, the early-exposed mice displayed a significant preference for a diet high in fat compared to controls. This effect was not due to diet familiarity as mice exposed to a novel high carbohydrate diet during this same early period failed to show differences in macronutrient preferences as adults. The increased intake of high fat diet in early exposed mice was specific to dietary preferences as no changes were detected for total caloric intake or caloric efficiency. Mechanistically, mice exposed to a high fat diet during early life exhibited significant alterations in biochemical markers of dopamine signaling in the nucleus accumbens, including changes in levels of phospho–dopamine and cyclic AMP-regulated phosphoprotein, molecular weight 32 kDa (DARPP-32) threonine-75, ΔFosB, and cyclin-dependent kinase 5. These results support our hypothesis that even brief early life exposure to calorically-dense palatable diets alters long-term programming of central mechanisms important in dietary preferences and reward. These changes may underlie the passive overconsumption of high fat foods contributing to the increasing body mass in the western world.

Section snippets

Animals and early diet exposure

Mice were generated on a mixed C57Bl/6:129 background as part of our in-house breeding colony. These mice have been on a mixed background population for more than 10 years (Bale et al., 2000), with introduction of a new gene pool every two years by breeding with an F1 C57Bl/6: 129 cross. At 3 weeks of age, litters were exposed to the high fat diet (Research Diets, New Brunswick, NJ, USA) for 1 week. The high fat diet contained 4.73 kcal/g and consisted of 44.9% fat, 35.1% carbohydrate, and 20%

Macronutrient choice preference

In order to determine how early diet exposure affected adult dietary preferences, mice exposed to a high fat diet from 3 to 4 weeks of age were examined for macronutrient choice preference for 10 days beginning at 3 months of age. Preference for the high fat diet (reported as the percent of total calories consumed as high fat diet; Fig. 1A) was significantly greater in mice that had been exposed to the high fat diet during early life (P<0.05). Preference for the high protein diet was not

Discussion

Studies of food preferences in infants and children have shown that early exposure to different flavors can lead to increased acceptance of and preferences for these flavors in later life (Liem and Mennella 2002, Mennella and Beauchamp 2002). As children are increasingly exposed to foods high in fat during early life, it is important to determine how exposure to certain diets during this time may affect food preferences during adulthood and be a possible contributing factor to the increased

Conclusion

In conclusion, the present study demonstrates that a brief exposure to a palatable, high fat diet during early life programs an increased preference for this diet during adulthood that is not based on diet familiarity. Mechanistically, reduced DA signal transmission in the ventral striatum in these mice may result in an increased preference for the high fat diet in an attempt to normalize DA levels. The data then suggest that exposure to a palatable, high fat diet during early life may lead to

Acknowledgments

We thank K. Carlin for assistance with animal breeding and husbandry. This work was supported by the University of Pennsylvania Institute of Diabetes, Obesity and Metabolism, DK019525.

References (51)

  • T.E. Robinson et al.

    Structural plasticity associated with exposure to drugs of abuse

    Neuropharmacology

    (2004)
  • M.K. Serdula et al.

    Do obese children become obese adults?A review of the literature

    Prev Med

    (1993)
  • P.P. Silveira et al.

    Both infantile stimulation and exposure to sweet food lead to an increased sweet food ingestion in adult life

    Physiol Behav

    (2008)
  • S.L. Teegarden et al.

    Decreases in dietary preference produce increased emotionality and risk for dietary relapse

    Biol Psychiatry

    (2007)
  • S.L. Teegarden et al.

    Delta FosB-mediated alterations in dopamine signaling are normalized by a palatable high-fat diet

    Biol Psychiatry

    (2008)
  • D.M. Van den Heuvel et al.

    Getting connected in the dopamine system

    Prog Neurobiol

    (2008)
  • G.J. Wang et al.

    Brain dopamine and obesity

    Lancet

    (2001)
  • L. Zimmer et al.

    Chronic n-3 polyunsaturated fatty acid diet-deficiency acts on dopamine metabolism in the rat frontal cortex: a microdialysis study

    Neurosci Lett

    (1998)
  • U. Zippel et al.

    Altered action of dopamine and cholecystokinin on lateral hypothalamic neurons in rats raised under different feeding conditions

    Behav Brain Res

    (2003)
  • H.M. Abdolmaleky et al.

    Epigenetic alterations of the dopaminergic system in major psychiatric disorders

    Methods Mol Biol

    (2008)
  • T.L. Bale et al.

    Mice deficient for corticotropin-releasing hormone receptor-2 display anxiety-like behavior and are hypersensitive to stress

    Nat Genet

    (2000)
  • T.L. Bale et al.

    Corticotropin-releasing factor receptor-2-deficient mice display abnormal homeostatic responses to challenges of increased dietary fat and cold

    Endocrinology

    (2003)
  • L. Bellinger et al.

    Prenatal exposure to a maternal low-protein diet programmes a preference for high-fat foods in the young adult rat

    Br J Nutr

    (2004)
  • D.R. Benavides et al.

    Role of Cdk5 in drug abuse and plasticity

    Ann N Y Acad Sci

    (2004)
  • D.R. Benavides et al.

    Cdk5 modulates cocaine reward, motivation, and striatal neuron excitability

    J Neurosci

    (2007)
  • Cited by (99)

    • Behavioral profile of intermittent vs continuous access to a high fat diet during adolescence

      2019, Behavioural Brain Research
      Citation Excerpt :

      The aim of the present work was to evaluate the behavioral and cognitive differences observed in animals exposed to these two different patterns of fat administration. Although some studies report alterations after the cessation of an HFD on the reward system, such as a reduction in the dopaminergic signal and changes in gene expression [33–35,26]; and [28], only few studies have evaluated the behavioral effects of cessation of an HFD on cognitive behaviors. To address this issue, we employed adolescent mice, which either received a standard diet or had continuous or intermittent access to an HDF for 40 days.

    • Dissecting compulsive eating behavior into three elements

      2019, Compulsive Eating Behavior and Food Addiction: Emerging Pathological Constructs
    View all citing articles on Scopus
    1

    Current address: Department of Psychiatry, School of Medicine, 2401 TRL, University of Pennsylvania, 125 S. 31st Street, Philadelphia, PA 19104, USA.

    View full text