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母鼠亮氨酸丰富的饮食通过改善肌肉蛋白合成和降解的平衡来减少肿瘤荷瘤成年大鼠后代的肌肉质量损失。

Maternal Leucine-Rich Diet Minimises Muscle Mass Loss in Tumour-bearing Adult Rat Offspring by Improving the Balance of Muscle Protein Synthesis and Degradation.

机构信息

Laboratory of Nutrition and Cancer, Department of Structural and Functional Biology, Biology Institute, University of Campinas, UNICAMP, Rua Monteiro Lobato, 255, Campinas, São Paulo 13083862, Brazil.

出版信息

Biomolecules. 2019 Jun 13;9(6):229. doi: 10.3390/biom9060229.

DOI:10.3390/biom9060229
PMID:31200474
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6628133/
Abstract

Cachexia syndrome can affect cancer patients and new prevention strategies are required. Maternal nutritional supplementation can modify metabolic programming in the offspring, which lasts until adulthood. This could be a good approach against diseases such as cancer. A 3% leucine-rich diet treatment improved muscle protein turnover by modifying the mTOR and proteolytic pathways, thus we analysed whether maternal supplementation could ameliorate muscle protein turnover in adult offspring tumour-bearing rats. Pregnant Wistar rats received a control diet or 3% leucine-rich diet during pregnancy/lactation, and their weaned male offspring received a control diet until adulthood when they were distributed into following groups (n = 7-8 per group): C, Control; W, tumour-bearing; L, without tumour with a maternal leucine-rich diet; and WL, tumour-bearing with a maternal leucine-rich diet. Protein synthesis and degradation were assessed in the gastrocnemius muscle, focusing on the mTOR pathway, which was extensively altered in W group. However, the WL adult offspring showed no decrease in muscle weight, higher food intake, ameliorated muscle turnover, activated mTOR and p70S6K, and maintained muscle cathepsin H and calpain activities. Maternal leucine nutritional supplementation could be a positive strategy to improve muscle protein balance in cancer cachexia-induced muscle damage in adult offspring rats.

摘要

恶病质综合征会影响癌症患者,因此需要新的预防策略。母体营养补充可以改变后代的代谢编程,这种影响会持续到成年。这可能是对抗癌症等疾病的一种好方法。3%亮氨酸丰富的饮食治疗通过改变 mTOR 和蛋白水解途径来改善肌肉蛋白周转率,因此我们分析母体补充是否可以改善成年肿瘤荷瘤大鼠的肌肉蛋白周转率。怀孕的 Wistar 大鼠在怀孕/哺乳期接受对照饮食或 3%亮氨酸丰富的饮食,它们的雄性断奶后代在成年时接受对照饮食,直到成年时分为以下几组(每组 7-8 只):C,对照;W,荷瘤;L,无肿瘤,接受母体亮氨酸丰富的饮食;WL,肿瘤荷瘤,接受母体亮氨酸丰富的饮食。在比目鱼肌中评估蛋白质合成和降解,重点关注 mTOR 途径,W 组的 mTOR 途径发生了广泛改变。然而,WL 成年后代的肌肉重量没有下降,进食量更高,肌肉周转率得到改善,mTOR 和 p70S6K 被激活,肌肉组织组织蛋白酶 H 和钙蛋白酶的活性得以维持。母体亮氨酸营养补充可能是改善成年肿瘤恶病质诱导的肌肉损伤后代肌肉蛋白平衡的一种积极策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b21d/6628133/6bdd3e42077a/biomolecules-09-00229-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b21d/6628133/538de5790c84/biomolecules-09-00229-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b21d/6628133/0e151bc9b039/biomolecules-09-00229-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b21d/6628133/5ec3a40a49f4/biomolecules-09-00229-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b21d/6628133/113ed444c799/biomolecules-09-00229-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b21d/6628133/9d65a8609b11/biomolecules-09-00229-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b21d/6628133/6bdd3e42077a/biomolecules-09-00229-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b21d/6628133/538de5790c84/biomolecules-09-00229-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b21d/6628133/0e151bc9b039/biomolecules-09-00229-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b21d/6628133/5ec3a40a49f4/biomolecules-09-00229-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b21d/6628133/113ed444c799/biomolecules-09-00229-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b21d/6628133/9d65a8609b11/biomolecules-09-00229-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b21d/6628133/6bdd3e42077a/biomolecules-09-00229-g006.jpg

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本文引用的文献

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Inter-tissue communication in cancer cachexia.癌症恶病质中的组织间通讯。
Nat Rev Endocrinol. 2018 Dec;15(1):9-20. doi: 10.1038/s41574-018-0123-0.
2
Muscle regeneration is disrupted by cancer cachexia without loss of muscle stem cell potential.肌肉再生被癌症恶病质破坏,而肌肉干细胞潜能并未丧失。
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Maternal nutritional supplementation with fish oil and/or leucine improves hepatic function and antioxidant defenses, and minimizes cachexia indexes in Walker-256 tumor-bearing rats offspring.
妊娠与癌症:影响胎盘的细胞生物学及机制
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Nutrients. 2020 Jul 16;12(7):2106. doi: 10.3390/nu12072106.
给母鼠补充鱼油和/或亮氨酸可改善肝功能和抗氧化防御能力,并最大限度地减少 Walker-256 肿瘤荷瘤大鼠后代的恶病质指标。
Nutr Res. 2018 Mar;51:29-39. doi: 10.1016/j.nutres.2017.12.003. Epub 2017 Dec 28.
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L-leucine dietary supplementation modulates muscle protein degradation and increases pro-inflammatory cytokines in tumour-bearing rats.补充L-亮氨酸饮食可调节荷瘤大鼠的肌肉蛋白质降解并增加促炎细胞因子。
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Understanding cachexia as a cancer metabolism syndrome.将恶病质理解为一种癌症代谢综合征。
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