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

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 (D 2 O) 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.