Choi Eun Bee, Jeong Jae Hun, Jang Hye Min, Ahn Yu Jeong, Kim Kyu Hyeon, An Hyeong Seok, Lee Jong Youl, Jeong Eun Ae, Lee Jaewoong, Shin Hyun Joo, Kim Kyung Eun, Roh Gu Seob
Department of Anatomy and Convergence Medical Science, Bio Anti-Aging Medical Research Center, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, Korea.
Department of Medicine, College of Medicine, Gyeongsang National University, Jinju 52777, Gyeongnam, Korea.
Antioxidants (Basel). 2021 May 11;10(5):758. doi: 10.3390/antiox10050758.
Obesity and insulin resistance accelerate aging-related sarcopenia, which is associated with iron load and oxidative stress. Lipocalin-2 (LCN2) is an iron-binding protein that has been associated with skeletal muscle regeneration, but details regarding its role in obese sarcopenia remain unclear. Here, we report that elevated LCN2 levels in skeletal muscle are linked to muscle atrophy-related inflammation and oxidative stress in leptin-deficient ob/ob mice. RNA sequencing analyses indicated the gene expression is enhanced in skeletal muscle of ob/ob mice with sarcopenia. In addition to muscular iron accumulation in ob/ob mice, expressions of iron homeostasis-related divalent metal transporter 1, ferritin, and hepcidin proteins were increased in ob/ob mice compared to lean littermates, whereas expressions of transferrin receptor and ferroportin were reduced. Collectively, these findings demonstrate that LCN2 functions as a potent proinflammatory factor in skeletal muscle in response to obesity-related sarcopenia and is thus a therapeutic candidate target for sarcopenia treatment.
肥胖和胰岛素抵抗会加速与衰老相关的肌肉减少症，而这与铁负荷和氧化应激有关。脂质运载蛋白2（LCN2）是一种铁结合蛋白，与骨骼肌再生有关，但其在肥胖性肌肉减少症中的作用细节仍不清楚。在此，我们报告，瘦素缺乏的ob/ob小鼠骨骼肌中LCN2水平升高与肌肉萎缩相关的炎症和氧化应激有关。RNA测序分析表明，患有肌肉减少症的ob/ob小鼠骨骼肌中的基因表达增强。除了ob/ob小鼠肌肉中铁的积累外，与瘦小鼠相比，ob/ob小鼠中铁稳态相关的二价金属转运体1、铁蛋白和铁调素蛋白的表达增加，而转铁蛋白受体和铁转运蛋白的表达减少。总的来说，这些发现表明，LCN2在骨骼肌中作为一种有效的促炎因子，对肥胖相关的肌肉减少症作出反应，因此是肌肉减少症治疗的候选治疗靶点。
