Low-Carbohydrate Diet Exacerbates Denervation-Induced Atrophy of Rat Skeletal Muscle Under the Condition of Identical Protein Intake

IF 9.4 1区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Cachexia Sarcopenia and Muscle Pub Date : 2025-02-25 DOI:10.1002/jcsm.13738

Aki Yokogawa, Kohei Kido, Ikuru Miura, Eisuke Oyama, Daisuke Takakura, Keigo Tanaka, Daniel J. Wilkinson, Kenneth Smith, Philip J. Atherton, Kentaro Kawanaka

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Abstract

Background

While decreased protein intake is associated with muscle mass loss, it is unclear whether a decrease in carbohydrate intake adversely affects muscle atrophy independently of protein intake. Herein, we examined whether a low-carbohydrate (low-CHO) diet exacerbates denervation-induced muscle atrophy under conditions of identical protein intake.

Methods

On day one of the experiment, male Wistar rats underwent unilateral denervation. The contralateral leg was used as the control. After denervation, rats were divided into two dietary groups: high-carbohydrate (high-CHO) and low-CHO. Each group was fed a high-CHO (70% carbohydrate) or low-CHO (20% carbohydrate) diet over 7 days. Total protein and energy intakes in both groups were matched by pair feeding. Rats were provided with deuterium oxide (D₂O) tracer over the last 3 days of dietary intervention to quantify myofibrillar (muscle) protein synthesis (MPS).

Results

Denervation reduced wet weight of the gastrocnemius muscle compared to the contralateral control (p < 0.05). Reductions in gastrocnemius muscle weight were greater in the low-CHO group (−34%) than the high-CHO group (−28%) (p < 0.05). Although denervation decreased MPS compared to the contralateral control (p < 0.05), no dietary effect on MPS was observed. Denervation resulted in increased mRNA and protein expression of Atrogin-1, a ubiquitin E3 ligase, compared to that in the contralateral control (p < 0.05). Increases in Atrogin-1 gene and protein expression due to denervation were greater in the low-CHO group than in the high-CHO group (p < 0.05).

Conclusions

We conclude that a low-CHO diet may exacerbate denervation-induced atrophy in fast-twitch-dominant muscles compared to a high-CHO diet, even when the same protein intake is maintained. Although blunted MPS contributed to muscle atrophy due to denervation, exacerbation of muscle atrophy by the low-CHO diet was not accompanied by explanatory changes in MPS. The effect of the low-CHO diet might be related to promotion of muscle-specific ubiquitin E3 ligase gene expression.

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在相同蛋白质摄入条件下，低碳水化合物饮食加剧了失神经诱导的大鼠骨骼肌萎缩

虽然蛋白质摄入量的减少与肌肉质量损失有关，但目前尚不清楚碳水化合物摄入量的减少是否会独立于蛋白质摄入量对肌肉萎缩产生不利影响。在此，我们研究了在相同蛋白质摄入条件下，低碳水化合物（低cho）饮食是否会加剧去神经支配诱导的肌肉萎缩。方法实验第一天，雄性Wistar大鼠单侧去神经。以对侧腿为对照。去神经支配后，将大鼠分为高碳水化合物（高cho）和低cho两组。各组分别饲喂高cho（70%碳水化合物）或低cho（20%碳水化合物）日粮7 d。两组总蛋白质和总能量摄取量采用配对饲养。在饮食干预的最后3天给予大鼠氧化氘（D2O）示踪剂，以定量测定肌纤维蛋白合成（MPS）。结果与对侧对照组相比，去神经支配组腓肠肌湿重减轻（p < 0.05）。低cho组腓肠肌重量的减少（- 34%）大于高cho组（- 28%）（p < 0.05）。虽然与对侧对照组相比，去神经支配降低了MPS (p < 0.05)，但饮食对MPS没有影响。与对侧对照组相比，去神经支配导致泛素E3连接酶Atrogin-1 mRNA和蛋白表达增加（p < 0.05）。低cho组Atrogin-1基因和蛋白因去神经支配而表达的增加高于高cho组（p < 0.05）。我们的结论是，与高cho饮食相比，低cho饮食可能会加剧快速抽搐主导肌肉的去神经支配性萎缩，即使保持相同的蛋白质摄入量。虽然钝化的多磺酸粘多糖导致了肌肉萎缩，但低cho饮食导致的肌肉萎缩加剧并没有伴随着多磺酸粘多糖的解释性变化。低cho饮食的作用可能与促进肌肉特异性泛素E3连接酶基因表达有关。

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来源期刊

Journal of Cachexia Sarcopenia and Muscle MEDICINE, GENERAL & INTERNAL-

CiteScore

13.30

自引率

12.40%

发文量

234

审稿时长

16 weeks

期刊介绍： The Journal of Cachexia, Sarcopenia and Muscle is a peer-reviewed international journal dedicated to publishing materials related to cachexia and sarcopenia, as well as body composition and its physiological and pathophysiological changes across the lifespan and in response to various illnesses from all fields of life sciences. The journal aims to provide a reliable resource for professionals interested in related research or involved in the clinical care of affected patients, such as those suffering from AIDS, cancer, chronic heart failure, chronic lung disease, liver cirrhosis, chronic kidney failure, rheumatoid arthritis, or sepsis.