Dietary zinc deficiency disrupts skeletal muscle proteostasis and mitochondrial biology in rats

Abstract

ObjectivesZinc deficiency is related to reduced growth, mass, and work capacity of skeletal muscle. However, the underlying mechanisms in connection with skeletal muscle proteostasis and mitochondrial biology are not clear. The aim of this study was to investigate the consequences of dietary zinc deficiency on skeletal muscle proteostasis and mitochondrial biology in growing rats. MethodsThree-wk-old male Wistar/Kyoto weanling rats were fed either a zinc-deficient diet (<1 mg/kg; ad libitum) or a control diet pair-fed with zinc-deficient group (47.5 mg/kg) for a 7-wk period. Skeletal (gastrocnemius) muscle myofiber cross-sectional area was measured on hematoxylin and eosin-stained sections. Real-time quantitative reverse transcription polymerase chain reaction and immunoblotting were performed to study the target gene and protein expression, respectively. The chymotrypsin-like proteasomal activity was analyzed by fluorescence method. ResultsResults showed a decreased mean muscle fiber cross-sectional area and increased apoptosis in the muscle of zinc-deficient rats. Activation of the ubiquitin-proteasome system as indicated by increased levels of the E1 enzyme, MuRF1 (muscle-specific E3 ligase; muscle atrophy marker) and proteasomal activity was observed in the zinc-deficient rats. Declined autophagy (Beclin1, ATG5, and LC3), and increased endoplasmic reticulum stress markers were observed. Zinc deficiency also affected mitochondrial biology including fission, fusion, transcription, and oxidative phosphorylation components. ConclusionZinc deficiency disturbed the skeletal muscle proteostasis, and mitochondrial biology, causing decreased cell size and increased cell death.