Selenium Deficiency Dysregulates One-Carbon Metabolism in Nutritional Muscular Dystrophy of Chicks

Abstract

Background: Nutritional muscular dystrophy (NMD) in animals is induced by dietary selenium (Se) deficiency.

Objectives: This study was conducted to explore the underlying mechanism of Se deficiency-induced NMD in broilers.

Methods: One-day-old male Cobb broilers (n = 6 cages/diet, 6 birds/cage) were fed a Se-deficient diet (Se-Def, 47 μg Se/kg) or the Se-Def supplemented with 0.3 mg Se/kg (control) for 6 wk. Thigh muscles of broilers were collected at week 6 for measuring Se concentration, histopathology, and transcriptome and metabolome assays. The transcriptome and metabolome data were analyzed with bioinformatics tools and other data were analyzed with Student's t tests.

Results: Compared with the control, Se-Def induced NMD in broilers, including reduced (P < 0.05) final body weight (30.7%) and thigh muscle size, reduced number and cross-sectional area of fibers, and loose organization of muscle fibers. Compared with the control, Se-Def decreased (P < 0.05) the Se concentration in the thigh muscle by 52.4%. It also downregulated (P < 0.05) GPX1, SELENOW, TXNRD1-3, DIO1, SELENOF, H, I, K, M, and U by 23.4-80.3% in the thigh muscle compared with the control. Multi-omics analyses indicated that the levels of 320 transcripts and 33 metabolites were significantly altered (P < 0.05) in response to dietary Se deficiency. Integrated transcriptomics and metabolomics analysis revealed that one-carbon metabolism, including the folate and methionine cycle, was primarily dysregulated by Se deficiency in the thigh muscles of broilers.

Conclusions: Dietary Se deficiency induced NMD in broiler chicks, potentially with the dysregulation of one-carbon metabolism. These findings may provide novel treatment strategies for muscle disease.

Keywords: Se deficiency; broilers; folate cycle; methionine cyclefolate cycle; nutritional muscular dystrophy; one-carbon metabolism.