Department of Health, Human Performance and Recreation, Baylor University, Waco, TX 76798, USA.
Department of Biology, Baylor University, Waco, TX 76798, USA.
Appl Physiol Nutr Metab. 2022 May;47(5):555-564. doi: 10.1139/apnm-2021-0764. Epub 2022 Feb 11.
Obesity-associated inflammation and/or oxidative stress can damage intramuscular proteins and jeopardize muscle integrity. The immunoproteasome (iProt) is vital to remove oxidatively modified proteins, but this function may be compromised with obesity. We sought to elucidate whether diet-induced obesity alters intramuscular iProt content and activity in mice to identify a possible mechanism for impaired muscle proteostasis in the obese state. Total proteasome content and activity and estimates of muscle oxidative damage, inflammation, muscle mass and strength were also assessed. Twenty-three male, 5-week-old C57BL/6J mice were fed a high-fat, high-sucrose (HFS; 45% kcal fat, 17% sucrose, = 12) or low-fat, low-sucrose (LFS; 10% kcal fat, 0% sucrose, = 11) diet for 12 weeks. Strength was assessed via a weightlifting test. Despite no change in pro-inflammatory cytokines ( > 0.05), oxidative protein damage was elevated within the gastrocnemius ( = 0.036) and tibialis anterior ( = 0.033) muscles of HFS-fed mice. Intramuscular protein damage coincided with reduced iProt and total proteasome activity ( < 0.05), and reductions in relative muscle mass ( < 0.001). Therefore, proteasome dysregulation occurs in obese muscle and may be a critical link in muscle oxidative stress. Our results show for the first time that immunoproteasome and total proteasome function is significantly reduced within obese muscle. Visceral fat mass is a significant predictor of diminished proteasome activity in skeletal muscle. Proteasome function is inversely correlated with an intramuscular accumulation of oxidatively damaged proteins.
肥胖相关的炎症和/或氧化应激会损害肌内蛋白质，危及肌肉完整性。免疫蛋白酶体（iProt）对于清除氧化修饰的蛋白质至关重要，但这种功能可能会因肥胖而受损。我们试图阐明饮食诱导的肥胖是否会改变小鼠肌内 iProt 含量和活性，以确定肥胖状态下肌肉蛋白质稳态受损的可能机制。还评估了总蛋白酶体含量和活性以及肌肉氧化损伤、炎症、肌肉质量和力量的估计值。23 只 5 周龄雄性 C57BL/6J 小鼠分别喂食高脂肪高蔗糖（HFS；45%热量脂肪，17%蔗糖， = 12）或低脂低蔗糖（LFS；10%热量脂肪，0%蔗糖， = 11）饮食 12 周。通过举重测试评估力量。尽管促炎细胞因子没有变化（ > 0.05），但 HFS 喂养小鼠的比目鱼肌（ = 0.036）和胫骨前肌（ = 0.033）中的氧化蛋白损伤升高。肌内蛋白质损伤与 iProt 和总蛋白酶体活性降低（ < 0.05）以及相对肌肉质量减少（ < 0.001）相一致。因此，蛋白酶体失调发生在肥胖肌肉中，可能是肌肉氧化应激的关键环节。我们的研究结果首次表明，免疫蛋白酶体和总蛋白酶体功能在肥胖肌肉中显著降低。内脏脂肪量是骨骼肌蛋白酶体活性降低的一个重要预测因素。蛋白酶体功能与肌内氧化损伤蛋白的积累呈负相关。
