RESUMO
To better understand the role of irisin in humans, we examined the effects of irisin in human primary adipocytes and fresh human subcutaneous white adipose tissue (scWAT). Human primary adipocytes derived from 28 female donors' fresh scWAT were used to examine the effects of irisin on browning and mitochondrial respiration, and preadipocytes were used to examine the effects of irisin on adipogenesis and osteogenesis. Cultured fragments of scWAT and perirenal brown fat were used for investigating signal transduction pathways that mediate irisin's browning effect by Western blotting to detect phosphorylated forms of p38, ERK, and STAT3 as well as uncoupling protein 1 (UCP1). Individual responses to irisin in scWAT were correlated with basal expression levels of brown/beige genes. Irisin upregulated the expression of browning-associated genes and UCP1 protein in both cultured primary mature adipocytes and fresh adipose tissues. It also significantly increased thermogenesis at 5 nmol/l by elevating cellular energy metabolism (OCR and ECAR). Treating human scWAT with irisin increased UCP1 expression by activating the ERK and p38 MAPK signaling. Blocking either pathway with specific inhibitors abolished irisin-induced UCP1 upregulation. However, our results showed that UCP1 in human perirenal adipose tissue was insensitive to irisin. Basal levels of brown/beige and FNDC5 genes correlated positively with the browning response of scWAT to irisin. In addition, irisin significantly inhibited adipogenic differentiation but promoted osteogenic differentiation. We conclude that irisin promotes "browning" of mature white adipocytes by increasing cellular thermogenesis, whereas it inhibits adipogenesis and promotes osteogenesis during lineage-specific differentiation. Our findings provide a rationale for further exploring the therapeutic use of irisin in obesity and exercise-associated bone formation.
Assuntos
Adipócitos Brancos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Fibronectinas/farmacologia , Mitocôndrias/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , RNA Mensageiro/efeitos dos fármacos , Termogênese/efeitos dos fármacos , Adipócitos Marrons/efeitos dos fármacos , Adipócitos Marrons/metabolismo , Adipócitos Brancos/metabolismo , Adipogenia/genética , Adolescente , Adulto , Idoso , Western Blotting , Respiração Celular/efeitos dos fármacos , Células Cultivadas , Exercício Físico , MAP Quinases Reguladas por Sinal Extracelular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Obesidade/metabolismo , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteogênese/genética , Fosfoproteínas/efeitos dos fármacos , Fosfoproteínas/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Fator de Transcrição STAT3/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Gordura Subcutânea/citologia , Termogênese/genética , Proteína Desacopladora 1/efeitos dos fármacos , Proteína Desacopladora 1/metabolismo , Regulação para Cima , Adulto Jovem , Proteínas Quinases p38 Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Brown-Sequard syndrome (BSS) produced by cervical disc disorders has rarely been seen clinically and only 50 cases have been reported in English literatures. However, most of which have resulted from acute disc herniation. Here, we report a case of BSS produced by calcified herniated C4-C5 disc and posterior vertebral osteophyte, in which decompression through anterior approach was performed. This case revealed the potential of cervical spondylopathy leading to BSS in a chronic manner. Once the diagnosis is established, it is advisable to perform decompression as early as possible.