ABSTRACT
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.
Subject(s)
Adipocytes, White/drug effects , Adipogenesis/drug effects , Cell Differentiation/drug effects , Fibronectins/pharmacology , Mitochondria/drug effects , Osteogenesis/drug effects , RNA, Messenger/drug effects , Thermogenesis/drug effects , Adipocytes, Brown/drug effects , Adipocytes, Brown/metabolism , Adipocytes, White/metabolism , Adipogenesis/genetics , Adolescent , Adult , Aged , Blotting, Western , Cell Respiration/drug effects , Cells, Cultured , Exercise , Extracellular Signal-Regulated MAP Kinases/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Female , Humans , Immunohistochemistry , Middle Aged , Mitochondria/metabolism , Obesity/metabolism , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteogenesis/genetics , Phosphoproteins/drug effects , Phosphoproteins/metabolism , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , STAT3 Transcription Factor/drug effects , STAT3 Transcription Factor/metabolism , Signal Transduction , Subcutaneous Fat/cytology , Thermogenesis/genetics , Uncoupling Protein 1/drug effects , Uncoupling Protein 1/metabolism , Up-Regulation , Young Adult , p38 Mitogen-Activated Protein Kinases/drug effects , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
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.
