Ren Yanru, Wang Kun, Wu Yuanyuan, Li Jiarui, Ma Jie, Wang Lijuan, Zhang Chenglei, Li Jianning, Wei Yanhong, Yang Yi
Ningxia Regional Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Regional High Incidence Disease, Ningxia Medical University, Yinchuan 750004, China; Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education (Ningxia Medical University), Ningxia Medical University, Yinchuan 750004, China; School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China; Department of Endocrinology, General Hospital of Ningxia Medical University, Yinchuan 750004, China.
School of Basic Medical Sciences, Ningxia Medical University, Yinchuan 750004, China.
Int J Biol Macromol. 2025 Apr;301:140488. doi: 10.1016/j.ijbiomac.2025.140488. Epub 2025 Jan 29.
Sarcopenic obesity (SO) defined as the coexistence of obesity and sarcopenia. While the anti-obesity effects of Lycium barbarum polysaccharide (LBP), the main component of L. barbarum extract, are known, its efficacy against SO remains unexplored. Consequently, we aimed to investigate the therapeutic effects of LBP on SO and the elucidate the underlying mechanisms. Our results revealed that LBP administration decreased obesity-related factors, and increased muscle-related factors in mice fed a high-fat diet (HFD). LBP administration ameliorated PA- and HFD-induced hyperglycaemia by modulating IRS-1 and GLUT-4 levels while also mitigating the ectopic fat deposition. Furthermore, our results demonstrated that LBP can mitigate mitochondrial structural abnormalities and dysfunction-characterized by increased mitochondrial membrane potential and ATP levels, reduced reactive oxygen species levels-through the activation of mitophagy. However, these beneficial effects of LBP on skeletal muscle were negated by AMPK inhibitor and siRNA knockdown of Parkin expression. Taken together, our findings indicate that LBP may effectively modulate glucose and lipid metabolism while ameliorating skeletal muscle atrophy via the activation of the AMPK/PINK1/Parkin-mediated mitophagy pathway, thereby repairing the mitochondrial structure and function. Consequently, LBP emerges as a promising therapeutic candidate for addressing obesity-related impacts on skeletal muscle.
肌少症性肥胖（SO）定义为肥胖与肌少症并存。虽然枸杞提取物的主要成分枸杞多糖（LBP）的抗肥胖作用已为人所知，但其对SO的疗效仍未得到探索。因此，我们旨在研究LBP对SO的治疗作用并阐明其潜在机制。我们的结果显示，在喂食高脂饮食（HFD）的小鼠中，给予LBP可降低肥胖相关因子，并增加肌肉相关因子。给予LBP通过调节胰岛素受体底物-1（IRS-1）和葡萄糖转运蛋白4（GLUT-4）水平改善了棕榈酸（PA）和HFD诱导的高血糖症，同时还减轻了异位脂肪沉积。此外，我们的结果表明，LBP可通过激活线粒体自噬减轻线粒体结构异常和功能障碍，其特征为线粒体膜电位和ATP水平升高、活性氧水平降低。然而，LBP对骨骼肌的这些有益作用被AMPK抑制剂和Parkin表达的小干扰RNA（siRNA）敲低所抵消。综上所述，我们的研究结果表明，LBP可能通过激活AMPK/PINK1/Parkin介导的线粒体自噬途径有效调节葡萄糖和脂质代谢，同时改善骨骼肌萎缩，从而修复线粒体结构和功能。因此，LBP成为解决肥胖对骨骼肌相关影响的有前景的治疗候选物。
