11/1/2015. Background. Fructose metabolism and neural correlates of food reactivity in obese children

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1 Fructose metabolism and neural correlates of food reactivity in obese children JENNIFER S. LAURENT, PhD, FNP 7 TH ANNUAL NURSING RESEARCH & EVIDENCE-BASED PRACTICE SYMPOSIUM NOVEMBER 5-6, 2015 No financial disclosures or conflicts of interest. Background Obesity rates in adolescents have doubled since 1970, with nearly 21% being diagnosed as clinically obese. 1 Studies of children have found a relationship between excessive consumption of sugar- sweetened beverages (SSB) and obesity. 2 Consumption of fructose has increased 22% since Adolescents are heavy consumers of SSB sweetened primarily with high fructose corn syrup (HFCS; 55/45). 2,3 Adolescents ingest upwards of 100 grams per day in such beverages, 43% of their total daily caloric intake. 4 1

2 Why Fructose? Fructose has similar metabolic and detrimental effects on the brain and gut as does ethanol. 4 lipogenesis, 5 gluconeogenesis, 5 hepatic steatosis and inflammation, 6,7 and stimulation of the neural reward circuit. 8,9 Children are particularly sensitive to sweet foods and demonstrate greater reward sensitivity for high sugar foods. 10 Obese children appear to have greater reward sensitivity to sugar than lean children. 10 Neural Reward Circuit Gambling Food Sex Cocaine Alcohol Heroin Chocolate Internet a priori Hypothesis The metabolic profile of fructose may play a key role in obese children s development of addictive-like eating and thus, the development and perpetuation of obesity in a subset of at-risk children. Purpose To determine how the metabolic profile of fructose affects neural reward and cognitive control circuits in obese children and how that relates to phenotypic traits of addictive-like eating. 2

3 Study Design Cross-sectional year olds Clinically obese Healthy otherwise 3 study visits to the CRC Assented & consented Fructose dose: 1 gm/kg of IBW, max 75 gm Methods Screening & Phenotypic Measures Fructose Drink -> Serial blood, breath, and urine samples Fructose Drink -> frmi DD Food Stroop Go/No-go DD SST Measures of Addictive-Like Eating Yale Food Addiction Scale 11 child version (YFASc) Food addiction symptom count and diagnostic threshold Food craving inventory 12 (FCI) Power of Food Scale child version 13 (c-pfs) Appetitive responsiveness in food abundant environments Yale Food Addiction Scale-child Loss of Control Inability to Cut Down Large Amount of Time Spent Tolerance Withdrawal Given up on Activities Clinically Significant Impairment or Distress 3+ symptoms plus Clinical Sig => Food addiction 3

4 Findings N=16 2 non-completers 3 scored as food addicted 4 scored with addictive-like eating (YFASc) but did not meet full criteria for FA 9 scored without addictivelike eating. 8 females/8 males 1 Black; 2 Native American; 13 White Ages Mean BMI 36.7 Mean fructose dose 59.5 gm. ~2 cans of soda <½ Big Gulp <½ Slurpee Findings (n=14) Addictive-like eating correlated (YFASc) (p<.05) with greater appetitive responsiveness (c-pfs) and greater craving of carbohydrates and overall cravings independent of body mass index (BMI), age, and gender. BMI scores were significantly (p<.02) related to the frequency that the subjects gave in to their cravings and ate fats, carbohydrates, and sweets. No correlation was found between fructose levels, YFASc, BMIz score, gender, and age. No correlation was found between YFASc and ventral striatal response to oral fructose load. Findings Serum Fructose C max (μm ) Peak serum fructose v. Ventral striatal activity on Food Stroop task Serum fructose, but not glucose, peak concentration (Cmax) was significantly and positively correlated with activation in the ventral striatum in response to the food cues (p<.001) Ventral Striatum Activation (AU) 4

5 Findings Fructose, but not glucose, time to peak (Tmax) was negatively correlated with the striatal response to food cues (p=.023). Fructose T max (m minutes) Serum fructose time to peak v. Ventral striatum activation on Food Stroop task Ventral Striatum Activation (AU) Conclusions The VS response to fructose demonstrated a pattern of effects that is consistent with abuse potential of drugs leading to dependence (e.g. alcohol, cocaine). The lack of VS response to glucose suggests that different sugars affect neural reward mechanisms differently. Ingestion of fructose may have an important role in shaping the brain s reward response to food stimuli. Future Directions Limitations Replication using HFCS [55:45] that is more consistent with the general populations consumption of fructose. Examining the effect of refined sugars on the gut brain axis to better understand neurobiological mechanism contributing to obesity in children. Sample size Lack of lean controls No baseline fmri State v. Trait??? 5

6 Research Team Co-Investigators: Hugh Garavan, PhD Paula Deming, PhD Jillian Sullivan, MD, MS Joshua Nickerson, MD Research Assistants: Karen Wierstall, PhD Mitchell Snow Mariam Haq Katie Brennan Kasey C. Olds Funding: College of Nursing and Health Sciences Incentive Grant & Klifa Foundation Special Acknowledgements: University of Vermont Clinical Research Center University of Vermont Center for Biomedical Imaging References 1. Ogden CL, Carroll MD, Kit BK & Flegal KM. Prevalence of childhood and adult obesity in the United States, JAMA 311, (2014). 2. Ludwig, D. S., Peterson, K. E. & Gortmaker, S. L. Relation between consumption of sugar-sweetened drinks and childhood obesity: a prospective, observational analysis. Lancet 357, (2001). 3. Lustig, R. H. Fructose: metabolic, hedonic, and societal parallels with ethanol. J. Am. Diet. Assoc. 110, (2010). 4. Havel, P. J. Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr. Rev. 63, (2005). 5. Cawley, N. X. Sugar making sugar: gluconeogenesis triggered by fructose via a hypothalamic-adrenal-corticosterone circuit. Endocrinology 153, (2012). 6. Vos, M. B. & Lavine, J. E. Dietary fructose in nonalcoholic fatty liver disease. Hepatology 57, (2013). 7. Jin, R. et al. Children with NAFLD are more sensitive to the adverse metabolic effects of fructose beverages than children without NAFLD. J. Clin. Endocrinol. Metab. 97, E1088 E1098 (2012). 8. Erlanson-Albertsson, C. How palatable food disrupts appetite regulation. Basic Clin. Pharmacol. Toxicol. 97, (2005). 9. Pelchat, M. L. Of human bondage: food craving, obsession, compulsion, and addiction. Physiol. Behav. 76, (2002). 10. Spear, L. The behavioral neuroscience of adolescence. (W. W. Norton, 2010). 11. Gearhardt, A. N., Roberto, C. A., Seamans, M. J., Corbin, W. R. & Brownell, K. D. Preliminary validation of the Yale Food Addiction Scale for children. Eat. Behav. 12. White M.A., Whisenhunt B.L., Williamson D.A., Greenway F.L., Netemeyer R.G. Development and validation of the food-craving inventory. Obesity. 2002;10(2): Laurent, J. S. Psychometric properties for the Children s Power of Food Scale in a diverse sample of pre-adolescent youth. Appl. Nurs. Res. doi: /j.apnr , (2013). 6