Konstanze Miehle1, Thomas Ebert2, Susan Kralisch2, Annett Hoffmann3, Jürgen Kratzsch4, Haiko Schlögl3, Michael Stumvoll3, Mathias Fasshauer2. 1. Department of Internal Medicine (Endocrinology and Nephrology), University of Leipzig, Germany. Electronic address: konstanze.miehle@medizin.uni-leipzig.de. 2. Department of Internal Medicine (Endocrinology and Nephrology), University of Leipzig, Germany; Leipzig University Medical Center, IFB AdiposityDiseases, Leipzig, Germany. 3. Department of Internal Medicine (Endocrinology and Nephrology), University of Leipzig, Germany. 4. Institute for Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University of Leipzig, Germany.
Abstract
OBJECTIVE: Patients 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 METHODS: Circulating 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. RESULTS: Median FGF21 serum concentrations were significantly higher in LD patients (381.2ng/l) as compared to the control group (231.2ng/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. CONCLUSIONS: Serum 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.
OBJECTIVE:Patients 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-humanimmunodeficiency virus (HIV) LD. MATERIAL AND METHODS: Circulating 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. RESULTS: Median FGF21 serum concentrations were significantly higher in LD patients (381.2ng/l) as compared to the control group (231.2ng/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. CONCLUSIONS: Serum 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.
Authors: Dionysios V Chartoumpekis; Yoko Yagishita; Marco Fazzari; Dushani L Palliyaguru; Uma Nm Rao; Apostolos Zaravinos; Nicholas Kh Khoo; Francisco J Schopfer; Kurt R Weiss; George K Michalopoulos; Ian Sipula; Robert M O'Doherty; Thomas W Kensler; Nobunao Wakabayashi Journal: JCI Insight Date: 2018-03-08
Authors: Ricardo Moure; Pere Domingo; Joan Villarroya; Laura Gasa; José M Gallego-Escuredo; Tania Quesada-López; Samantha Morón-Ros; Alberto F Maroto; Gracia M Mateo; Joan C Domingo; Francesc Villarroya; Marta Giralt Journal: Antimicrob Agents Chemother Date: 2018-05-25 Impact factor: 5.191