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The possible role of astrocytes in the regulation of feeding has been overlooked. It is well-established that the endothelial cells constituting the blood-brain barrier transport leptin from blood to brain and that hypothalamic neurons respond to leptin to induce anorexic signaling. However, few studies have addressed the role of astrocytes in either leptin(More)
We recently reported that mouse astrocytes express leptin receptors (ObR), and that obesity induces upregulation of astrocytic ObR. To provide further evidence of the importance of astrocytic ObR expression, we performed double-labeling fluorescent in situ hybridization (FISH) and immunohistochemistry in the rat hypothalamus. Laser confocal microscopic(More)
The blood-brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new(More)
Nesfatin-1 is an 82 amino acid peptide that suppresses food intake after intracerebroventricular injection. Nesfatin-1 and its precursor NUCB2 were identified by subtraction cloning in cell lines of both neuronal and adipocytic origin. This provides a strong basis for studies to determine how peripherally derived nesfatin-1 permeates the blood-brain barrier(More)
FGF21 recently has been proposed as a missing link in the biology of fasting, raising the question of whether it directly reaches the brain. We used multiple time-regression analysis to quantify the influx rate of this polypeptide across the blood-brain barrier (BBB), size-exclusion chromatography to examine degradation, capillary depletion to differentiate(More)
Interleukin-15 (IL-15) is a cytokine produced in the normal brain that acts on its specific receptor IL-15Rα and co-receptors IL-2Rβ and IL-2Rγ in neuronal cells. The functions of the cerebral IL-15 system, however, are not yet clear. To test the hypothesis that IL-15Rα regulates metabolic activity and body temperature, we quantified the specific metabolic(More)
Evidence both from mice and cultured cells suggests an important role of soluble leptin receptors in obesity and leptin signaling. However, the direct effects of soluble receptors on leptin uptake by cells are not clear. This study shows that soluble leptin receptors antagonize the permeation of leptin across the mouse blood-brain barrier by reducing the(More)
Reactive gliosis, a sign of neuroinflammation, has been observed in mice with adult-onset obesity as well as CNS injury. The hypothesis that obesity-derived metabolic factors exacerbate reactive gliosis in response to mechanical injury was tested here on cultured primary glial cells subjected to a well-established model of scratch wound injury. Cells(More)
Interleukin (IL)-15 is a ubiquitously expressed cytokine that in the basal state is mainly localized intracellularly, including the nucleus. Unexpectedly, tumor necrosis factor-α (TNF) time-dependently induced nuclear export of IL-15Rα and IL15. This process was inhibited by leptomycine B (LMB), a specific inhibitor of nuclear export receptor chromosomal(More)
Peptides are able to cross the blood–brain barrier (BBB) through various mechanisms, opening new diagnostic and therapeutic avenues. However, their BBB transport data are scattered in the literature over different disciplines, using different methodologies reporting different influx or efflux aspects. Therefore, a comprehensive BBB peptide database(More)