RESUMO
OBJECTIVE: In rodents, brown (BAT) and white (WAT) adipose tissues are targets and expression sites for fibroblast growth factor-21 (FGF21). In contrast, human WAT expresses negligible levels of FGF21. We examined FGF21 expression in human BAT samples, including the induced BAT found in adult patients with pheochromocytoma, and interscapular and visceral BAT from newborns. METHODS: The expression of FGF21 and uncoupling protein-1 (UCP1, a brown adipocyte marker), was determined by quantitative real-time-PCR and immunoblotting. The transcript levels of marker genes for developmentally-programmed BAT (zinc-finger-protein of the cerebellum-1, ZIC1) and inducible-BAT (cluster of differentiation-137, CD137) were also determined. RESULTS: FGF21 and UCP1 are significantly expressed in visceral adipose tissue from pheochromocytoma patients, but not in visceral fat from healthy individuals. In neonates, FGF21 and UCP1 are both expressed in visceral and interscapular fat, and their expression levels show a significant positive correlation. Marker gene expression profiles suggest that inducible BAT is present in visceral fat from pheochromocytoma patients and neonates, whereas developmentally-programmed BAT is present in neonatal interscapular fat. CONCLUSIONS: Human BAT, but not WAT, expresses FGF21. The expression of FGF21 is especially high in inducible, also called beige/brite, neonatal BAT, but it is also found in the interscapular, developmentally-programmed, BAT of neonates.
Assuntos
Adipócitos Marrons/metabolismo , Tecido Adiposo Marrom/metabolismo , Neoplasias das Glândulas Suprarrenais/genética , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Feocromocitoma/genética , Ligante 4-1BB/genética , Ligante 4-1BB/metabolismo , Tecido Adiposo Branco/metabolismo , Neoplasias das Glândulas Suprarrenais/metabolismo , Adulto , Idoso , Feminino , Humanos , Recém-Nascido , Canais Iônicos/genética , Canais Iônicos/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Feocromocitoma/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transcriptoma/genética , Proteína Desacopladora 1RESUMO
OBJECTIVE: The receptor for advanced glycation end products, RAGE, plays an important role in the pathogenesis of several diseases. sRAGE, soluble receptor for advanced glycation end products, is an inhibitor of the pathological effect mediated via RAGE. The aim of this study was to assess the usefulness of measuring sRAGE concentration in pregnant women with threatening preterm labor. METHODS: Serum levels of sRAGE, interleukin-6 (IL-6) and routine markers of inflammation were determined in 46 pregnant women with threatening preterm labor, 35 healthy pregnant women and 15 non-pregnant controls. RESULTS: Serum levels of sRAGE in healthy pregnant women were significantly lower than in non-pregnant controls (669+/-296 vs. 1929+/-727 pg/mL, P<0.05). Women with threatening preterm birth had a significantly higher concentration of serum sRAGE in comparison with healthy pregnant women (819+/-329 pg/mL vs. 669+/-296 pg/mL, P<0.05). Conversely, patients with PPROM had significantly lower levels of sRAGE compared with patients with threatening premature labor (600+/-324 pg/mL, P<0.05). sRAGE correlated negatively with leukocyte counts (r=-0.325, P<0.05). CONCLUSIONS: sRAGE might be a new and promising marker of premature labor, especially with the symptoms of PPROM.
Assuntos
Produtos Finais de Glicação Avançada/sangue , Trabalho de Parto Prematuro/sangue , Receptores Imunológicos/sangue , Adulto , Biomarcadores/sangue , Feminino , Ruptura Prematura de Membranas Fetais/sangue , Humanos , Inflamação/sangue , Interleucina-6/sangue , Projetos Piloto , Gravidez , Complicações Infecciosas na Gravidez/sangue , Receptor para Produtos Finais de Glicação AvançadaRESUMO
We seek to understand the mechanism for the delayed postnatal switch between glycolytic and oxidative metabolism in preterm newborns. Our previous study [Brauner et al. (Pediatr Res 53: 691-697, 2003)] suggested impaired postnatal recruitment of the gene for mitochondrial uncoupling protein 3 (UCP3) by nutritional lipids in skeletal muscle of neonates delivered before approximately 26 wk of gestation. UCP3 is linked to lipid oxidation and may be involved in the defective development of energy metabolism in skeletal muscles of very preterm newborns. In extension of our previous study, autopsy samples of musculus quadriceps femoris from 40 mostly preterm neonates and 5 fetuses were used for quantification of transcripts for UCP3, GLUT4, and their transcriptional regulator, AMP-activated protein kinase (AMPK). The new analysis confirmed the defect in the recruitment of the UCP3 gene expression by lipids in very preterm neonates. It also suggested involvement of AMPK in the control of expression of both metabolic genes, UCP3 and GLUT4, in the skeletal muscle of the newborns. Experiments on adult C57BL/6J mice confirmed the relationships between the transcripts and supported the involvement of AMPK in the control of UCP3 gene expression.