Alterations in mouse Hypothalamic adipokine gene expression and leptin signaling following chronic spinal cord injury and with advanced age

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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 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.

Original languageEnglish
Article numbere41073
JournalPLoS One
Volume7
Issue number7
DOIs
StatePublished - Jul 16 2012

Fingerprint

adipokines
Adipokines
Leptin
leptin
Spinal Cord Injuries
Gene expression
spinal cord
Gene Expression
gene expression
mice
cardiovascular diseases
Cardiovascular Diseases
Endoplasmic Reticulum Stress
endoplasmic reticulum
Chemical activation
resistin
endocrine diseases
Resistin
Endocrine System Diseases
Leptin Receptors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Alterations in mouse Hypothalamic adipokine gene expression and leptin signaling following chronic spinal cord injury and with advanced age. / Bigford, Gregory E.; Bracchi-Ricard, Valerie C.; Nash, Mark S; Bethea, John R.

In: PLoS One, Vol. 7, No. 7, e41073, 16.07.2012.

Research output: Contribution to journalArticle

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