alterations in mouse hypothalamic adipokine gene expression and leptin signaling following chronic spinal cord injury and with advanced age改变老鼠的下丘脑adipokine基因表达和瘦素信号后慢性脊髓损伤和老年.pdfVIP

Alterations in Mouse Hypothalamic Adipokine Gene Expression and Leptin Signaling following Chronic Spinal Cord Injury and with Advanced Age 1 1 1,2,3 1,2 Gregory E. Bigford *, Valerie C. Bracchi-Ricard , Mark S. Nash , John R. Bethea 1The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, Florida, United States of America, 2 The Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, United States of America, 3 The Department of Rehabilitation Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States of America Abstract Chronic spinal cord injury (SCI) results in an accelerated trajectory of several cardiovascular disease (CVD) risk factors and related aging characteristics, however the molecular mechanisms that are activated have not been explored. Adipokines and leptin signaling are known to play a critical role in neuro-endocrine regulation of energy metabolism, and are now implicated in central inflammatory processes associated with CVD. Here, we examine hypothalamic adipokine gene expression and leptin signaling in response to chronic spinal cord injury and with advanced age. We demonstrate significant changes in fasting-induced adipose factor (FIAF), resistin (Rstn), long-form leptin receptor (LepRb) and suppressor of cytokine-3 (SOCS3) gene expression following chronic SCI and with advanced age. LepRb and Jak2/stat3 signaling is significantly decreased and the leptin signaling inhibitor SOCS3 is significantly elevated with chronic SCI and advanced age. In addition, we investigate endoplasmic reticulum (ER) stress and activation of the uncoupled protein respo