title: Fibroblast growth factor-21, body composition, and insulin resistance in pre-pubertal and early pubertal males and females.
abstract: OBJECTIVE
  Accumulating evidence derived primarily from animal models suggests that fibroblast growth factor-21 (FGF-21) may affect the musculoskeletal system via effects on the capacity of tissues to respond to insulin. A proportion of musculoskeletal properties and underpinnings of promoting/preventing insulin resistance are established early in the pubertal transition. Thus, the objective of this study was to test the hypothesis that insulin resistance and/or obesity will promote greater FGF-21 concentration which will be inversely associated with musculoskeletal parameters [lean mass and bone mineral content (BMC)] in pre-/early pubertal children. Given the sexual dimorphic nature of musculoskeletal development of fat mass accrual, differences by obesity status and sex were also investigated.
  
  
  METHODS
  Cross-sectional.
  
  
  METHODS
  Children ages 7-12 years (n = 69, 38% male, 48% non-Hispanic black, 45% obese).
  
  
  METHODS
  Fasting FGF-21, glucose and insulin measures were obtained. An estimate of insulin resistance was derived using the homoeostatic model assessment of insulin resistance (HOMA-IR). Body composition (BMC, lean mass and fat mass) was assessed by DXA. Multivariate regression analysis was used to evaluate the influence of FGF-21 on BMC, lean mass and HOMA-IR as dependent variables. Obesity status was established based on BMI z-score.
  
  
  RESULTS
  FGF-21 concentrations did not differ by obesity status or by sex. There was an inverse association between FGF-21 and BMC among nonobese individuals (P = 0·01) and an inverse association between FGF-21 and lean mass among females (P = 0·02), which were both independent of fat mass. FGF-21 was inversely associated with HOMA-IR in males, but not females (P = 0·04).
  
  
  CONCLUSIONS
  The existence of relationships of FGF-21 with musculoskeletal parameters and insulin resistance raises the possibility of crosstalk between these systems. These findings suggest that circulating FGF-21 may differ in its association with bone, lean mass and insulin resistance depending on sex and weight status.
authors.affiliation: Children's Hospital of Alabama, University of Alabama at Birmingham (UAB), Birmingham, AL, USA.
authors.forename: Lynae J
authors.initials: LJ
authors.lastname: Hanks
authors.forename: Krista
authors.initials: K
authors.lastname: Casazza
authors.forename: Ambika P
authors.initials: AP
authors.lastname: Ashraf
authors.forename: Stephenie
authors.initials: S
authors.lastname: Wallace
authors.forename: Orlando M
authors.initials: OM
authors.lastname: Gutiérrez
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D015992:Body Mass Index; D001835:Body Weight; D015519:Bone Density; D002648:Child; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D009765:Obesity / Q000503:physiopathology; D011627:Puberty; D012044:Regression Analysis; D012737:Sex Factors; D012741:Sexual Maturation
chemical_list: D001786:Blood Glucose; D007328:Insulin; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors