Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, United States.
Department of Physical Therapy and Athletic Training, University of Utah, Salt Lake City, UT, United States.
J Nutr. 2023 Oct;153(10):2915-2928. doi: 10.1016/j.tjnut.2023.08.033. Epub 2023 Aug 29.
Metabolic diseases are often associated with muscle atrophy and heightened inflammation. The whey bioactive compound, glycomacropeptide (GMP), has been shown to exhibit anti-inflammatory properties and therefore may have potential therapeutic efficacy in conditions of skeletal muscle inflammation and atrophy.
The purpose of this study was to determine the role of GMP in preventing lipotoxicity-induced myotube atrophy and inflammation.
C2C12 myoblasts were differentiated to determine the effect of GMP on atrophy and inflammation and to explore its mechanism of action in evaluating various anabolic and catabolic cellular signaling nodes. We also used a lipidomic analysis to evaluate muscle sphingolipid accumulation with the various treatments. Palmitate (0.75 mM) in the presence and absence of GMP (5 μg/mL) was used to induce myotube atrophy and inflammation and cells were collected over a time course of 6-24 h.
After 24 h of treatment, GMP prevented the palmitate-induced decrease in the myotube area and myogenic index and the increase in the TLR4-mediated inflammatory genes tumor necrosis factor-α and interleukin 1β. Moreover, phosphorylation of Erk1/2, and gene expression of myostatin, and the E3 ubiquitin ligases, FBXO32, and MuRF1 were decreased with GMP treatment. GMP did not alter palmitate-induced ceramide or diacylglycerol accumulation, muscle insulin resistance, or protein synthesis.
In summary, GMP prevented palmitate-induced inflammation and atrophy in C2C12 myotubes. The GMP protective mechanism of action in muscle cells during lipotoxic stress may be related to targeting catabolic signaling associated with cellular stress and proteolysis but not protein synthesis.
代谢疾病常伴有肌肉萎缩和炎症加剧。乳清生物活性化合物糖巨肽（GMP）具有抗炎特性，因此在骨骼肌炎症和萎缩的情况下可能具有潜在的治疗效果。
本研究旨在确定 GMP 在预防脂毒性诱导的肌管萎缩和炎症中的作用。
C2C12 成肌细胞分化，以确定 GMP 对萎缩和炎症的影响，并探索其在评估各种合成代谢和分解代谢细胞信号节点中的作用机制。我们还使用脂质组学分析来评估各种处理方法下肌肉鞘脂的积累。用棕榈酸（0.75 mM）和（或）GMP（5 μg/mL）处理诱导肌管萎缩和炎症，并在 6-24 h 的时间过程中收集细胞。
治疗 24 h 后，GMP 可防止棕榈酸诱导的肌管面积和肌生成指数下降，以及 TLR4 介导的炎症基因肿瘤坏死因子-α和白细胞介素 1β增加。此外，GMP 处理可降低 Erk1/2 的磷酸化以及肌肉生长抑制素、E3 泛素连接酶 FBXO32 和 MuRF1 的基因表达。GMP 不改变棕榈酸诱导的神经酰胺或二酰基甘油积累、肌肉胰岛素抵抗或蛋白质合成。
总之，GMP 可预防 C2C12 肌管中棕榈酸诱导的炎症和萎缩。GMP 在脂肪毒性应激下对肌肉细胞的保护作用机制可能与靶向与细胞应激和蛋白水解相关的分解代谢信号有关，但与蛋白质合成无关。
