Characterization of growth differentiation factor 15 (GDF15) as a neurotropic adipokine permeable to the brain
Abstract GDF15 (growth/differentiation factor-15) belongs to the superfamily of transforming growth factor-beta. Little is known about adipocytic regulation of GDF15, its concentrations in serum and cerebrospinal fluid (CSF), its permeability to the brain, and its correlation with neurological disea...
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Nature Portfolio
2025-08-01
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| Online Access: | https://doi.org/10.1038/s41598-025-14846-8 |
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| author | Andreas Schmid Emily Wilfurth Alexandra Höpfinger Manuel Behrendt Edita Islami Thomas Karrasch Martin Berghoff Andreas Schäffler |
| author_facet | Andreas Schmid Emily Wilfurth Alexandra Höpfinger Manuel Behrendt Edita Islami Thomas Karrasch Martin Berghoff Andreas Schäffler |
| author_sort | Andreas Schmid |
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| description | Abstract GDF15 (growth/differentiation factor-15) belongs to the superfamily of transforming growth factor-beta. Little is known about adipocytic regulation of GDF15, its concentrations in serum and cerebrospinal fluid (CSF), its permeability to the brain, and its correlation with neurological diseases. This knowledge is important for a potential and clinical role of GDF15 as a mediator of the fat-brain axis in metabolic and neurological diseases. GDF15 mRNA expression in 3T3-L1 adipocytes was measured by qPCR and GDF15 protein levels in supernatants, serum and CSF were determined by ELISA. In vitro, GDF15 expression is nearly absent in pre-adipocytes and strongly upregulated during adipocyte differentiation. Insulin upregulates GDF15 secretion in adipocytes under normo- and hyperglycemic conditions. In vivo, we quantified GDF15 protein concentrations in paired samples of serum and CSF in a large and well-characterized clinical cohort of n = 390 patients undergoing neurological investigation and spinal puncture. This broad data set could serve as a basis for the development of GDF15 reference values in serum and CSF. GDF15 is highly permeable to the brain according to a specific CSF / serum ratio of 306 × 10–3. GDF15 is significantly increased in overweight and type 2 diabetic patients and correlates positively with serum glucose and HbA1c. GDF15 in CSF is elevated in patients with increased CSF cell count and impaired blood–brain-barrier function. Among five subsets of neurological diagnoses, GDF15 is exclusively increased in CSF and serum of patients with infectious diseases. GDF15 represents a promising adipokine and mediator of the fat-brain-axis that is co-regulated with metabolic factors and elevated in neurological patients with infectious diseases. |
| format | Article |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-08-01 |
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| spelling | doaj-art-d43c1900b69c4bb0b1cf36898b63653c2025-08-20T03:44:06ZengNature PortfolioScientific Reports2045-23222025-08-0115111210.1038/s41598-025-14846-8Characterization of growth differentiation factor 15 (GDF15) as a neurotropic adipokine permeable to the brainAndreas Schmid0Emily Wilfurth1Alexandra Höpfinger2Manuel Behrendt3Edita Islami4Thomas Karrasch5Martin Berghoff6Andreas Schäffler7Department of Internal Medicine III, Giessen University HospitalDepartment of Internal Medicine III, Giessen University HospitalDepartment of Internal Medicine III, Giessen University HospitalDepartment of Internal Medicine III, Giessen University HospitalDepartment of Internal Medicine III, Giessen University HospitalDepartment of Internal Medicine III, Giessen University HospitalDepartment of Neurology, Giessen University HospitalDepartment of Internal Medicine III, Giessen University HospitalAbstract GDF15 (growth/differentiation factor-15) belongs to the superfamily of transforming growth factor-beta. Little is known about adipocytic regulation of GDF15, its concentrations in serum and cerebrospinal fluid (CSF), its permeability to the brain, and its correlation with neurological diseases. This knowledge is important for a potential and clinical role of GDF15 as a mediator of the fat-brain axis in metabolic and neurological diseases. GDF15 mRNA expression in 3T3-L1 adipocytes was measured by qPCR and GDF15 protein levels in supernatants, serum and CSF were determined by ELISA. In vitro, GDF15 expression is nearly absent in pre-adipocytes and strongly upregulated during adipocyte differentiation. Insulin upregulates GDF15 secretion in adipocytes under normo- and hyperglycemic conditions. In vivo, we quantified GDF15 protein concentrations in paired samples of serum and CSF in a large and well-characterized clinical cohort of n = 390 patients undergoing neurological investigation and spinal puncture. This broad data set could serve as a basis for the development of GDF15 reference values in serum and CSF. GDF15 is highly permeable to the brain according to a specific CSF / serum ratio of 306 × 10–3. GDF15 is significantly increased in overweight and type 2 diabetic patients and correlates positively with serum glucose and HbA1c. GDF15 in CSF is elevated in patients with increased CSF cell count and impaired blood–brain-barrier function. Among five subsets of neurological diagnoses, GDF15 is exclusively increased in CSF and serum of patients with infectious diseases. GDF15 represents a promising adipokine and mediator of the fat-brain-axis that is co-regulated with metabolic factors and elevated in neurological patients with infectious diseases.https://doi.org/10.1038/s41598-025-14846-8GDF15Cerebrospinal fluidFat-Brain axisAdipocyteAdipose tissueAdipokine |
| spellingShingle | Andreas Schmid Emily Wilfurth Alexandra Höpfinger Manuel Behrendt Edita Islami Thomas Karrasch Martin Berghoff Andreas Schäffler Characterization of growth differentiation factor 15 (GDF15) as a neurotropic adipokine permeable to the brain Scientific Reports GDF15 Cerebrospinal fluid Fat-Brain axis Adipocyte Adipose tissue Adipokine |
| title | Characterization of growth differentiation factor 15 (GDF15) as a neurotropic adipokine permeable to the brain |
| title_full | Characterization of growth differentiation factor 15 (GDF15) as a neurotropic adipokine permeable to the brain |
| title_fullStr | Characterization of growth differentiation factor 15 (GDF15) as a neurotropic adipokine permeable to the brain |
| title_full_unstemmed | Characterization of growth differentiation factor 15 (GDF15) as a neurotropic adipokine permeable to the brain |
| title_short | Characterization of growth differentiation factor 15 (GDF15) as a neurotropic adipokine permeable to the brain |
| title_sort | characterization of growth differentiation factor 15 gdf15 as a neurotropic adipokine permeable to the brain |
| topic | GDF15 Cerebrospinal fluid Fat-Brain axis Adipocyte Adipose tissue Adipokine |
| url | https://doi.org/10.1038/s41598-025-14846-8 |
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