title: Fibroblast growth factor 21 levels in young healthy females display day and night variations and are increased in response to short-term energy deprivation through a leptin-independent pathway.
abstract: OBJECTIVE
  Fibroblast growth factor (FGF)-21 is an endocrine factor with potent metabolic effects. Its day-night patterns of secretion and/or its physiological response to energy deprivation and relationship to free fatty acids (FFAs) and/or leptin remain to be fully elucidated. We aim to elucidate day-night pattern of FGF-21 levels and its relationship to FFA, to assess whether energy deprivation alters its circulating patterns, and to examine whether leptin may mediate these changes.
  
  
  METHODS
  Six healthy lean females were studied for 72 h in a cross-over interventional study under three different conditions: on isocaloric diet and in a fasting state with administration of either placebo or metreleptin in physiological replacement doses. Blood samples were obtained hourly from 8:00 a.m. on day 4 until 8:00 a.m. on day 5.
  
  
  RESULTS
  FGF-21 exhibited day-night variation pattern during the isocaloric fed state. Fasting significantly increased FGF-21 levels (P < 0.01) via a leptin-independent pathway. Day-night variation pattern in the fed state was lost on fasting. Leptin replacement in the hypoleptinemic state restored approximate entropy of FGF-21 time series but did not alter circulating levels. FGF-21 levels were closely cross-correlated with FFA levels in all three states.
  
  
  CONCLUSIONS
  A day-night variation in the levels of FGF-21 exists in young lean females in the fed state. Energy deprivation increases FGF-21 levels via a leptin-independent pathway. The interaction between FGF-21 and starvation-induced lipolysis, as indicated by its close cross-correlations with FFA in both fed state and energy deprivation, needs to be studied further.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Joo-Pin
authors.initials: JP
authors.lastname: Foo
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Aronis
authors.forename: John P
authors.initials: JP
authors.lastname: Chamberland
authors.forename: Jason
authors.initials: J
authors.lastname: Paruthi
authors.forename: Hyun-Seuk
authors.initials: HS
authors.lastname: Moon
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D000328:Adult; D057906:Circadian Clocks / Q000187:drug effects / Q000502:physiology*; D004734:Energy Metabolism / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D020738:Leptin / Q000031:analogs & derivatives / Q000097:blood* / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D055815:Young Adult
chemical_list: D005230:Fatty Acids, Nonesterified; D020738:Leptin; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; C415771:metreleptin