BACKGROUND We have recently shown that a novel signalling kinase, inositol hexakisphosphate kinase 1 (IP6K1), is implicated in whole-body insulin resistance via its inhibitory action on Akt. Insulin and insulin like growth factor 1 (IGF-1) share many intracellular processes with both known to play a key role in glucose and protein metabolism in skeletal muscle. AIMS We aimed to compare IGF/IP6K1/Akt signalling and the plasma proteomic signature in individuals with a range of BMIs after ingestion of lean meat. METHODS Ten lean [Body mass index (BMI) (in kg/m2): 22.7 ± 0.4; Homeostatic model assessment of insulin resistance (HOMAIR): 1.36 ± 0.17], 10 overweight (BMI: 27.1 ± 0.5; HOMAIR: 1.25 ± 0.11), and 10 obese (BMI: 35.9 ± 1.3; HOMAIR: 5.82 ± 0.81) adults received primed continuous L-[ring-13C6]phenylalanine infusions. Blood and muscle biopsy samples were collected at 0 min (post-absorptive), 120 min and 300 min relative to the ingestion of 170 g pork loin (36 g protein and 5 g fat) to examine skeletal muscle protein signalling, plasma proteomic signatures, and whole-body phenylalanine disappearance rates (Rd). RESULTS Phenylalanine Rd was not different in obese compared to lean individuals at all time points and was not responsive to a pork ingestion (basal, P = 0.056; 120 & 300 min, P > 0.05). IP6K1 was elevated in obese individuals at 120 min post-prandial vs basal (P < 0.05). There were no acute differences plasma proteomic profiles between groups in the post-prandial state (P > 0.05). CONCLUSIONS These data demonstrate, for the first time that muscle IP6K1 protein content is elevated after lean meat ingestion in obese adults, suggesting that IP6K1 may be contributing to the dysregulation of nutrient uptake in skeletal muscle. In addition, proteomic analysis showed no differences in proteomic signatures between obese, overweight or lean individuals.

中文翻译：

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摄入瘦肉会增加患有肥胖症的年轻人的肌肉肌醇六磷酸磷酸激酶1蛋白含量，而与餐后循环蛋白质组不同。

背景技术我们最近显示，一种新型的信号激酶，肌醇六磷酸激酶1（IP6K1），通过对Akt的抑制作用而参与了全身胰岛素抵抗。胰岛素和胰岛素样生长因子1（IGF-1）具有许多细胞内过程，已知两者都在骨骼肌的葡萄糖和蛋白质代谢中起关键作用。目的我们旨在比较瘦肉摄入后一系列BMI个体的IGF / IP6K1 / Akt信号转导和血浆蛋白质组学特征。方法十个瘦[身体质量指数（BMI）（kg / m2）：22.7±0.4; 胰岛素抵抗的稳态模型评估（HOMAIR）：1.36±0.17]，超重10（BMI：27.1±0.5; HOMAIR：1.25±0.11）和10肥胖（BMI：35.9±1.3; HOMAIR：5.82±0.81）成年人已接受灌注连续输注L- [ring-13C6]苯丙氨酸。相对于摄入170 g猪里脊肉（36 g蛋白和5 g脂肪）在0分钟（吸收后），120分钟和300分钟采集血液和肌肉活检样品，以检查骨骼肌蛋白信号传导，血浆蛋白质组学特征，和全身苯丙氨酸消失率（Rd）。结果在所有时间点，与瘦肉个体相比，苯丙氨酸Rd在肥胖者中没有差异，并且对猪肉摄入没有反应（基础，P = 0.056； 120和300 min，P> 0.05）。餐后120分钟相对于基础餐，肥胖个体的IP6K1升高（P <0.05）。餐后状态的各组之间血浆蛋白质组学特征无急性差异（P> 0.05）。结论这些数据首次证明，肥胖成年人摄入瘦肉后，肌肉IP6K1蛋白含量增加，提示IP6K1可能是骨骼肌营养摄入异常的原因。此外，蛋白质组学分析显示，肥胖，超重或瘦者之间的蛋白质组学特征没有差异。