Alterations in Mouse Hypothalamic Adipokine Gene Expression and Leptin Signaling following Chronic Spinal Cord Injury and with Advanced AgeReportar como inadecuado




Alterations in Mouse Hypothalamic Adipokine Gene Expression and Leptin Signaling following Chronic Spinal Cord Injury and with Advanced Age - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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 response UPR as a biological hallmark of leptin resistance. We observe the activation of the ER stress-UPR proteins IRE1, PERK, and eIF2alpha, demonstrating leptin resistance in chronic SCI and with advanced age. These findings provide evidence for adipokine-mediated inflammatory responses and leptin resistance as contributing to neuro-endocrine dysfunction and CVD risk following SCI and with advanced age. Understanding the underlying mechanisms contributing to SCI and age related CVD may provide insight that will help direct specific therapeutic interventions.



Autor: Gregory E. Bigford , Valerie C. Bracchi-Ricard, Mark S. Nash, John R. Bethea

Fuente: http://plos.srce.hr/



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