A. Yokogawa, K. Kido, I. Miura, E. Oyama, D. Takakura, K. Tanaka, DJ. Wilkinson, K. Smith, PJ. Atherton, et al. (2025). Low-Carbohydrate Diet Exacerbates Denervation-Induced Atrophy of Rat Skeletal Muscle Under the Condition of Identical Protein Intake. Journal of cachexia, sarcopenia and muscle, 16(2), e13738. https://doi.org/10.1002/jcsm.13738

PubMed 40000911

[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.