title: Expression of fibroblast growth factor-21 in muscle is associated with lipodystrophy, insulin resistance and lipid disturbances in patients with HIV.
abstract: BACKGROUND
  Fibroblast growth factor (FGF)-21 is a novel regulator of glucose and lipid metabolism. Recently, increased FGF-21 mRNA expression in muscle was found in patients with type 2 diabetes, but the role for FGF-21 in muscle is not well understood. Patients with HIV-infection and lipodystrophy are characterised by various degree of lipid-driven insulin resistance. We hypothesized that muscle FGF-21 mRNA would be altered in HIV patients with lipodystrophy.
  
  
  METHODS
  Twenty-five HIV-infected men with lipodystrophy (LD) and 15 age-matched healthy controls, received an oral glucose tolerance test and a euglycemic-hyperinsulinemic clamp (50 mU/m2/min) combined with 6,6-H2 glucose infusion. Muscle biopsies were obtained and FGF-21 mRNA and glycogen synthase (GS) activity were measured.
  
  
  RESULTS
  Subjects with HIV were insulin resistant compared with non-HIV subjects. Compared to controls, HIV subjects demonstrated a twofold increase of plasma FGF-21 from 70.4±56.8 pg/ml vs 109.1±71.8 pg/ml, respectively (p = 0.04) and an eight-fold increase in muscular FGF-21 mRNA expression (p = 0.001). Muscle FGF-21 mRNA correlated inversely with the rate of disappearance of glucose during insulin clamp (r = -0.54, p = 0.0009), and the GS fractional velocity in muscle (r = -0.39, p = 0.03), and directly with fasting insulin (r = 0.50, p = 0.0022), HOMA-IR (r = 0.47, p = 0.004), triglycerides (r = 0.60. P = 0.0001), waist-to-hip ratio (r = 0.51, p = 0.0001) and limb fat mass (-0.46, p = 0.004), but not to plasma FGF-21.
  
  
  CONCLUSIONS
  FGF-21 mRNA is increased in skeletal muscle in HIV patients and correlates to whole-body (primarily reflecting muscle) insulin resistance, but not to plasma FGF-21. Those findings add to the evidence that FGF-21 is a myokine and may suggest that muscle FGF-21 is working in a local manner.
authors.affiliation: Centre of Inflammation and Metabolism, Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark. blm@rh.dk
authors.forename: Birgitte
authors.initials: B
authors.lastname: Lindegaard
authors.forename: Thine
authors.initials: T
authors.lastname: Hvid
authors.forename: Thomas
authors.initials: T
authors.lastname: Grøndahl
authors.forename: Christian
authors.initials: C
authors.lastname: Frosig
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
authors.forename: Pernille
authors.initials: P
authors.lastname: Hojman
authors.forename: Bente Klarlund
authors.initials: BK
authors.lastname: Pedersen
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008060:Lipodystrophy / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*
chemical_list: C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors