Fibroblast growth factor 21 decreases after liver fat reduction via growth hormone augmentation

Growth Horm IGF Res. 2017 Dec;37:1-6. doi: 10.1016/j.ghir.2017.10.002. Epub 2017 Oct 7.

Abstract

Objective: Fibroblast growth factor 21 (FGF21) ameliorates steatohepatitis but is increased in humans with fatty liver, potentially due to compensatory mechanisms and/or FGF21 resistance. Further, animal models suggest that GH increases serum FGF21. Tesamorelin, a growth hormone releasing hormone agonist, reduces liver fat in HIV-infected individuals. The objectives of this study were to investigate changes in FGF21 during tesamorelin treatment, to elucide the interplay between FGF21, GH augmentation, and liver fat reduction in humans.

Methods: 50 HIV-infected men and women with increased abdominal adiposity participated in this randomized, placebo-controlled trial of tesamorelin, 2mg vs. identical placebo daily for six months. Fasting laboratory measures, liver fat by 1H-magnetic resonance spectroscopy, and visceral adipose tissue (VAT) by computed tomography were obtained. Euglycemic hyperinsulinemic clamp was performed in a randomly selected subset.

Results: At baseline, serum log10 FGF21 was significantly associated with log10 liver fat (r=0.32, p=0.03). Log10 FGF21 tended to decrease in the tesamorelin group compared to placebo (p=0.06). Among the entire cohort, reductions in FGF21 were significantly associated with reductions in liver fat (ρ=0.41, p=0.01), log10 gamma glutamyl tran speptidase (GGT, r=0.40, p=0.009), and FIB4 index (r=0.37, p=0.02).

Conclusions: In HIV-infected individuals, FGF21 is significantly positively associated with liver fat. FGF21 decreases in association with reductions in liver fat, GGT, and FIB4, suggesting that FGF21 is upregulated in the context of steatosis and steatohepatitis and is reduced when these conditions improve. Moreover, these data suggest that tesamorelin improves liver fat via pathways other than increasing serum FGF21.

Trial registration: clinicaltrials.govNCT01263717.

Keywords: Fibroblast growth factor 21; Growth hormone releasing hormone; HIV; Liver fat; Tesamorelin.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adiposity
  • Adolescent
  • Adult
  • Aged
  • Fatty Liver / diagnostic imaging*
  • Female
  • Fibroblast Growth Factors / metabolism*
  • Gene Expression Regulation
  • Growth Hormone-Releasing Hormone / analogs & derivatives*
  • Growth Hormone-Releasing Hormone / pharmacology
  • HIV Infections / physiopathology*
  • Humans
  • Inflammation
  • Insulin-Like Growth Factor I / metabolism
  • Intra-Abdominal Fat / diagnostic imaging*
  • Magnetic Resonance Spectroscopy
  • Male
  • Middle Aged
  • Tomography, X-Ray Computed
  • Young Adult
  • gamma-Glutamyltransferase / metabolism

Substances

  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • Insulin-Like Growth Factor I
  • Growth Hormone-Releasing Hormone
  • gamma-Glutamyltransferase
  • gamma-glutamyltransferase, human
  • tesamorelin

Associated data

  • ClinicalTrials.gov/NCT01263717