High methionine diet in skeletal muscle remodeling- Epigenetic mechanism of homocysteine mediated growth retardation

Authors
M Singh, AK George, W Eyob et al

Lab
University of Louisville, Louisville, Kentucky, United States

Journal
Canadian Journal of Physiology and Pharmacology

Abstract
Epigenetic DNA methylation is crucial for gene-imprinting/off-printing ensuring epigenetic memory but generates copious homocysteine (Hcy) unequivocally. That is why during pregnancy mothers are recommended Ôfolic acidÕ to avoid birth-defects because of elevated Hcy levels (hyperhomocysteinemia; HHcy). Children born with HHcy have musculoskeletal abnormalities/growth retardation. We focus on gut-dysbiotic microbiome implication that instigates Ò1-carbon metabolismÓ and HHcy causing growth retardation along with muscle abnormalities. We test hypothesis whether high methionine diet (HMD, an amino acid high in red-meat) a substrate for Hcy can cause skeletal muscle and growth retardation and treatment with probiotics (PB) mitigate muscle dysfunction. We employed cystathionine beta synthase; CBS deficient mouse; CBS+/- fed with/without HMD and with/without a probiotic in drinking water for 16 weeks. Matrix metalloproteinase activity; a hallmark of remodeling was measured by zymography. Muscle functions were scored via electric stimulation. Our results suggest that compared to WT, CBS+/- mice exhibited reduced growth. MMP-2 activity was robust in CBS+/- and HMD effects were attenuated by PB intervention. Electrical stimulation magnitude was decreased in CBS+/- and CBS+/- treated with HMD. Interestingly; PB mitigated muscle growth retardation and atrophy. Collectively, results imply that individuals with mild/moderate HHcy seem more prone to skeletal muscle injury and its dysfunction

BIOSEB Instruments Used:
Grip strength test (BIO-GS3)