title: Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways.
abstract: OBJECTIVE
  Increases in fructose consumption have paralleled the increasing prevalence of obesity, and high-fructose diets are thought to promote weight gain and insulin resistance. Fructose ingestion produces smaller increases in circulating satiety hormones compared with glucose ingestion, and central administration of fructose provokes feeding in rodents, whereas centrally administered glucose promotes satiety.
  
  
  OBJECTIVE
  To study neurophysiological factors that might underlie associations between fructose consumption and weight gain.
  
  
  METHODS
  Twenty healthy adult volunteers underwent 2 magnetic resonance imaging sessions at Yale University in conjunction with fructose or glucose drink ingestion in a blinded, random-order, crossover design.
  
  
  METHODS
  Relative changes in hypothalamic regional cerebral blood flow (CBF) after glucose or fructose ingestion. Secondary outcomes included whole-brain analyses to explore regional CBF changes, functional connectivity analysis to investigate correlations between the hypothalamus and other brain region responses, and hormone responses to fructose and glucose ingestion.
  
  
  RESULTS
  There was a significantly greater reduction in hypothalamic CBF after glucose vs fructose ingestion (-5.45 vs 2.84 mL/g per minute, respectively; mean difference, 8.3 mL/g per minute [95% CI of mean difference, 1.87-14.70]; P = .01). Glucose ingestion (compared with baseline) increased functional connectivity between the hypothalamus and the thalamus and striatum. Fructose increased connectivity between the hypothalamus and thalamus but not the striatum. Regional CBF within the hypothalamus, thalamus, insula, anterior cingulate, and striatum (appetite and reward regions) was reduced after glucose ingestion compared with baseline (P < .05 significance threshold, family-wise error [FWE] whole-brain corrected). In contrast, fructose reduced regional CBF in the thalamus, hippocampus, posterior cingulate cortex, fusiform, and visual cortex (P < .05 significance threshold, FWE whole-brain corrected). In whole-brain voxel-level analyses, there were no significant differences between direct comparisons of fructose vs glucose sessions following correction for multiple comparisons. Fructose vs glucose ingestion resulted in lower peak levels of serum glucose (mean difference, 41.0 mg/dL [95% CI, 27.7-54.5]; P < .001), insulin (mean difference, 49.6 μU/mL [95% CI, 38.2-61.1]; P < .001), and glucagon-like polypeptide 1 (mean difference, 2.1 pmol/L [95% CI, 0.9-3.2]; P = .01).
  
  
  CONCLUSIONS
  In a series of exploratory analyses, consumption of fructose compared with glucose resulted in a distinct pattern of regional CBF and a smaller increase in systemic glucose, insulin, and glucagon-like polypeptide 1 levels.
authors.affiliation: Section of Endocrinology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8020, USA.
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Page
authors.forename: Owen
authors.initials: O
authors.lastname: Chan
authors.forename: Jagriti
authors.initials: J
authors.lastname: Arora
authors.forename: Renata
authors.initials: R
authors.lastname: Belfort-Deaguiar
authors.forename: James
authors.initials: J
authors.lastname: Dzuira
authors.forename: Brian
authors.initials: B
authors.lastname: Roehmholdt
authors.forename: Gary W
authors.initials: GW
authors.lastname: Cline
authors.forename: Sarita
authors.initials: S
authors.lastname: Naik
authors.forename: Rajita
authors.initials: R
authors.lastname: Sinha
authors.forename: R Todd
authors.initials: RT
authors.lastname: Constable
authors.forename: Robert S
authors.initials: RS
authors.lastname: Sherwin
mesh_terms: D000328:Adult; D000818:Animals; D001066:Appetite / Q000187:drug effects / Q000502:physiology; D001628:Beverages; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply* / Q000187:drug effects*; D018592:Cross-Over Studies; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1 / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006815:Hunger / Q000187:drug effects / Q000502:physiology; D007031:Hypothalamus / Q000098:blood supply / Q000187:drug effects; D007328:Insulin / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects*; D012201:Reward; D016037:Single-Blind Method
chemical_list: D007328:Insulin; D005632:Fructose; D052216:Glucagon-Like Peptide 1; D005947:Glucose