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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
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Arbit et al. (1970) studied this question.
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