Serum concentrations of fibroblast growth factor 21 are elevated in patients with congenital or acquired lipodystrophy

- Serum FGF21 is increased in lipodystrophy patients as compared to controls.
- FGF21 levels are associated with serum triglycerides and fibrate treatment.
- Potential sources for increased FGF21 are subcutaneous and brown adipose tissue.

ObjectivePatients with lipodystrophy (LD) suffer from loss of subcutaneous adipose tissue accompanied by dysregulation of several adipocyte-secreted factors. However, regulation of adipocyte-expressed fibroblast growth factor (FGF) 21 which acts in an insulin-mimetic, lipid-lowering, and anti-atherogenic manner has not been investigated in non-human immunodeficiency virus (HIV) LD.Material and methodsCirculating serum FGF21 levels were quantified in 37 patients with non-HIV LD and 37 controls matched for age, gender, and body mass index. Moreover, FGF21 plasma levels and mRNA expression were measured in LD mice and control animals. Additionally, serum FGF21 levels were assessed in 10 LD patients before and during metreleptin therapy.ResultsMedian FGF21 serum concentrations were significantly higher in LD patients (381.2 ng/l) as compared to the control group (231.2 ng/l; p = 0.023). There was an independent and positive association between circulating FGF21 and serum triglycerides (TG), as well as fibrate treatment, in multiple linear regression analysis. LD mice showed significantly upregulated FGF21 plasma levels (4.5-fold), as well as mRNA expression in various adipose tissue depots and liver as compared to controls (p < 0.05). Metreleptin treatment did not significantly alter circulating FGF21 levels in human subjects.ConclusionsSerum concentrations of FGF21 are elevated in patients with non-HIV LD with adipose tissue and liver being potential sources of increased production. TG and fibrate treatment are independent positive predictors of circulating FGF21.