The Belford Center for Spinal Cord Injury, College of Medicine, The Ohio State University, Columbus, OH 43210, USA; Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
Department of Neuroscience, College of Medicine, The Ohio State University, Columbus, OH 43210, USA; Neuroscience Graduate Program, The Ohio State University, Columbus, OH 43210, USA.
Exp Neurol. 2024 Sep;379:114847. doi: 10.1016/j.expneurol.2024.114847. Epub 2024 Jun 8.
Impaired sensorimotor functions are prominent complications of spinal cord injury (SCI). A clinically important but less obvious consequence is development of metabolic syndrome (MetS), including increased adiposity, hyperglycemia/insulin resistance, and hyperlipidemia. MetS predisposes SCI individuals to earlier and more severe diabetes and cardiovascular disease compared to the general population, which trigger life-threatening complications (e.g., stroke, myocardial infarcts). Although each comorbidity is known to be a risk factor for diabetes and other health problems in obese individuals, their relative contribution or perceived importance in propagating systemic pathology after SCI has received less attention. This could be explained by an incomplete understanding of MetS promoted by SCI compared with that from the canonical trigger diet-induced obesity (DIO). Thus, here we compared metabolic-related outcomes after SCI in lean rats to those of uninjured rats with DIO. Surprisingly, SCI-induced MetS features were equal to or greater than those in obese uninjured rats, including insulin resistance, endotoxemia, hyperlipidemia, liver inflammation and steatosis. Considering the endemic nature of obesity, we also evaluated the effect of premorbid obesity in rats receiving SCI; the combination of DIO + SCI exacerbated MetS and liver pathology compared to either alone, suggesting that obese individuals that sustain a SCI are especially vulnerable to metabolic dysfunction. Notably, premorbid obesity also exacerbated intraspinal lesion pathology and worsened locomotor recovery after SCI. Overall, these results highlight that normal metabolic function requires intact spinal circuitry and that SCI is not just a sensory-motor disorder, but also has significant metabolic consequences.
感觉运动功能障碍是脊髓损伤 (SCI) 的突出并发症。一个临床重要但不太明显的后果是代谢综合征 (MetS) 的发展，包括肥胖、高血糖/胰岛素抵抗和血脂异常。与一般人群相比，MetS 使 SCI 个体更容易更早且更严重地患上糖尿病和心血管疾病，这会引发危及生命的并发症（例如中风、心肌梗死）。尽管每种合并症已知是肥胖个体发生糖尿病和其他健康问题的危险因素，但它们在 SCI 后传播全身病理方面的相对贡献或感知重要性受到的关注较少。这可能是由于与经典的饮食诱导肥胖 (DIO) 相比，对 SCI 引起的 MetS 的认识不完整。因此，在这里我们比较了 SCI 后瘦大鼠与未受伤的 DIO 大鼠的代谢相关结果。令人惊讶的是，SCI 引起的 MetS 特征与肥胖未受伤大鼠的特征相等或更大，包括胰岛素抵抗、内毒素血症、血脂异常、肝炎症和脂肪变性。考虑到肥胖的流行性质，我们还评估了肥胖大鼠接受 SCI 前肥胖的影响；与单独 DIO 或 SCI 相比，DIO+SCI 的组合加剧了 MetS 和肝病理，表明患有 SCI 的肥胖个体特别容易发生代谢功能障碍。值得注意的是，肥胖前肥胖也加重了脊髓内病变的病理，并使 SCI 后的运动功能恢复恶化。总的来说，这些结果强调了正常代谢功能需要完整的脊髓回路，并且 SCI 不仅是一种感觉运动障碍，而且还有重大的代谢后果。
