Footnote:
Hinweis: Link zur Erstveröffentlichung URL: https://doi.org/10.3390/ijms21197214
Description:
Objective. Similar to obesity, lipodystrophy (LD) causes adipose tissue dysfunction and severe
metabolic complications. Growth differentiation factor 15 (GDF15) belongs to the transforming growth
factor superfamily and is dysregulated in metabolic disease including obesity and diabetes mellitus.
Circulating levels in LDand the impact of leptin treatment have not been investigated so far.Material and
Methods. GDF15 serum levels were quantified in 60 LD patients without human immunodeficiency
virus infection and 60 controlsmatched for age, gender, and bodymass index. The impact ofmetreleptin
treatment on circulating GDF15 was assessed in a subgroup of patients. GDF15 mRNA expression was
determined in metabolic tissues of leptin-deficient lipodystrophic aP2-nSREBP1c-Tg mice, obese ob/ob
mice, and control C57Bl6 mice. Results. Median GDF15 serum concentrations were significantly higher
in LD patients (819 ng/L) as compared to the control group (415 ng/L) (p < 0.001). In multiple linear
regression analysis, an independent and positive association remained between GDF15 on one hand and
age, patient group, hemoglobin A1c, triglycerides, and C-reactive protein on the other hand. Moreover,
there was an independent negative association between GFD15 and estimated glomerular filtration rate.
Circulating GDF15 was not significantly affected by metreleptin treatment in LD patients. Gdf15 was
upregulated in leptin-deficient lipodystrophic mice as compared to controls. Moreover, Gdf15 mRNA
expression was downregulated by leptin treatment in lipodystrophic and obese animals. Conclusions.
Serum concentrations of GDF15 are elevated in LD patients and independently associated withmarkers
of metabolic dysfunction. Gdf15 expression is higher in lipodystrophic mice and downregulated by
leptin treatment.