title: Metabolically protective cytokines adiponectin and fibroblast growth factor-21 are increased by acute overfeeding in healthy humans.
abstract: BACKGROUND
  Circulating levels of metabolically protective and adverse cytokines are altered in obese humans and rodent models. However, it is not clear whether these cytokines are altered rapidly in response to over-nutrition, or as a later consequence of the obese state.
  
  
  METHODS
  Forty sedentary healthy individuals were examined prior to and at 3 and 28 days of high fat overfeeding (+1250 kCal/day, 45% fat). Insulin sensitivity (hyperinsulinaemic-euglycaemic clamp), adiposity, serum levels of adiponectin and fibroblast growth factor-21 (FGF21), fatty acid binding protein-4 (FABP4), lipocalin-2 and plasminogen activator factor-1 (PAI1) were assessed. Statistics were performed by repeated measures ANOVA.
  
  
  RESULTS
  Overfeeding increased weight, body fat and liver fat, fasting glucose, insulin and reduced insulin sensitivity by clamp (all P <0.05). Metabolically protective cytokines, adiponectin and FGF21 were increased at day 3 of overfeeding (P ≤0.001) and adiponectin was also elevated at day 28 (P=0.001). FABP4, lipocalin-2 and PAI-1 were not changed by overfeeding at either time point.
  
  
  CONCLUSIONS
  Metabolically protective cytokines, adiponectin and FGF-21, were increased by over nutrition and weight gain in healthy humans, despite increases in insulin resistance. We speculate that this was in attempt to maintain glucose homeostasis in a state of nutritional excess. PAI-I, FABP4 and lipocalin 2 were not altered by overfeeding suggesting that changes in these cytokines may be a later consequence of the obese state.
  
  
  BACKGROUND
  www.clinicaltrials.gov (NCT00562393).
authors.affiliation: Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia ; Research Center for Reproductive Health, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Leonie K
authors.initials: LK
authors.lastname: Heilbronn
authors.forename: Lesley V
authors.initials: LV
authors.lastname: Campbell
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.forename: Dorit
authors.initials: D
authors.lastname: Samocha-Bonet
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism*; D050154:Adiposity; D000328:Adult; D016207:Cytokines / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D006963:Hyperphagia / Q000378:metabolism*; D007333:Insulin Resistance; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012737:Sex Factors; D055815:Young Adult
chemical_list: D000209:Acute-Phase Proteins; D052242:Adiponectin; D016207:Cytokines; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D017395:Plasminogen Activator Inhibitor 1; D011518:Proto-Oncogene Proteins; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors