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α2δ1-mediated maladaptive sensory plasticity disrupts adipose tissue homeostasis following spinal cord injury.

Debasish Roy | Elliot Dion | Jesse A Sepeda | Juan Peng | Sai Rishik Lingam | Kristy Townsend | Andrew Sas | Wenjing Sun | Andrea Tedeschi
Cell reports. Medicine | 2024

Spinal cord injury (SCI) increases the risk of cardiometabolic disorders, including hypertension, dyslipidemia, and insulin resistance. Not only does SCI lead to pathological expansion of adipose tissue, but it also leads to ectopic lipid accumulation in organs integral to glucose and insulin metabolism. The pathophysiological changes that underlie adipose tissue dysfunction after SCI are unknown. Here, we find that SCI exacerbates lipolysis in epididymal white adipose tissue (eWAT). Whereas expression of the α2δ1 subunit of voltage-gated calcium channels increases in calcitonin gene-related peptide-positive dorsal root ganglia neurons that project to eWAT, conditional deletion of the gene encoding α2δ1 in these neurons normalizes eWAT lipolysis after SCI. Furthermore, α2δ1 pharmacological blockade through systemic administration of gabapentin also normalizes eWAT lipolysis after SCI, preventing ectopic lipid accumulation in the liver. Thus, our study provides insight into molecular causes of maladaptive sensory processing in eWAT, facilitating the development of strategies to reduce metabolic and cardiovascular complications after SCI.

Pubmed ID: 38663398 RIS Download

Antibodies used in this publication

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: P30 CA016058
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS110681
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS124714

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