Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
Department of Surgery, Viborg Regional Hospital, Viborg, Denmark.
Am J Clin Nutr. 2021 Sep 1;114(3):1159-1172. doi: 10.1093/ajcn/nqab148.
β-lactoglobulin (BLG) stimulates muscle protein synthesis and β-hydroxybutyrate (BHB) inhibits muscle breakdown. Whether combining the 2 can additively attenuate disease-induced muscle loss is unknown.
Based on previous observations of anticatabolic effects of protein and ketone bodies during inflammation, and using a novel model combining ongoing systemic inflammation, fasting, and immobilization, we tested whether the anticatabolic muscle response to oral amino acids is altered compared with control conditions, as well as whether coadministration of oral BHB and BLG further improves the muscle anabolic response. Muscle net balance (NBphe) was the primary outcome and intramyocellular signals were assessed.
In a randomized crossover design, 8 young men underwent either preconditioning with LPS (prestudy day: 1 ng/kg, study day: 0.5 ng/kg) combined with a 36-h fast and bed rest to mimic catabolic inflammatory disease (CAT) or an overnight fast (control [CTR]) prior to isocaloric nutritional interventions on 3 occasions separated by ∼6 wk (range 42 to 83 d).
NBphe increased similarly upon all conditions (interaction P = 0.65). From comparable baseline rates, both Rdphe [muscle synthesis, median ratio (95% CI): 0.44 (0.23, 0.86) P = 0.017] and Raphe [muscle breakdown, median ratio (95% CI): 0.46 (0.27, 0.78) P = 0.005] decreased following BHB + BLG compared with BLG. BLG increased Rdphe more under CAT conditions compared with CTR (interaction P = 0.02). CAT increased inflammation, energy expenditure, and lipid oxidation and decreased Rdphe and anabolic signaling [mammalian target of rapamycin (mTOR) and eukaryotic translation initiation factor 4E-binding protein 1 (4EPB1) phosphorylation].
In contrast to our initial hypothesis, NBphe increased similarly following BLG during CAT and CTR conditions; CAT however, specifically stimulated the BLG-mediated increase in protein synthesis, whereas BHB coadministration did not affect NBphe, but distinctly dampened the BLG-induced increase in muscle amino acid fluxes thereby liberating circulating amino acids for anabolic actions elsewhere.
β-乳球蛋白（BLG）可刺激肌肉蛋白合成，β-羟丁酸（BHB）可抑制肌肉分解。目前尚不清楚同时使用这两种物质是否能累加性地减轻疾病引起的肌肉损失。
基于之前观察到的蛋白和酮体在炎症期间的抗分解代谢作用，以及使用一种新的模型，将持续的全身炎症、禁食和固定相结合，我们检测了与对照条件相比，口服氨基酸对肌肉的抗分解代谢反应是否发生改变，以及同时给予口服 BHB 和 BLG 是否能进一步改善肌肉合成代谢反应。肌肉净平衡（NBphe）是主要结局指标，同时评估了细胞内信号。
在一项随机交叉设计中，8 名年轻男性接受了 LPS 预处理（预研究日：1ng/kg，研究日：0.5ng/kg），并进行 36 小时禁食和卧床休息，以模拟分解代谢性炎症疾病（CAT），或在 3 次等热量营养干预前进行一夜禁食（对照[CTR]），这 3 次干预间隔约 6 周（42 至 83 天）。
在所有条件下，NBphe 的增加均相似（交互 P=0.65）。从可比的基线率来看，Rdphe[肌肉合成，中位数比值（95%CI）：0.44（0.23，0.86）P=0.017]和 Raphe[肌肉分解，中位数比值（95%CI）：0.46（0.27，0.78）P=0.005]在 BHB+BLG 后均低于 BLG。与 CTR 相比，BLG 在 CAT 条件下增加 Rdphe 的效果更好（交互 P=0.02）。CAT 增加了炎症、能量消耗和脂质氧化，并降低了 Rdphe 和合成代谢信号[哺乳动物雷帕霉素靶蛋白（mTOR）和真核翻译起始因子 4E 结合蛋白 1（4EPB1）磷酸化]。
与我们最初的假设相反，在 CAT 和 CTR 条件下，BLG 同样能增加 NBphe；然而，CAT 特别刺激了 BLG 介导的蛋白质合成增加，而 BHB 联合使用并不影响 NBphe，但明显抑制了 BLG 诱导的肌肉氨基酸通量增加，从而释放出循环氨基酸用于其他部位的合成代谢作用。
