July 25, 2021

BETACH3

Hypothesis: Betaine decreases the pathogenicity of Covid-19.

Betaine Delayed Muscle Loss by Attenuating Samtor Complex Inhibition for mTORC1 Signaling via Increasing SAM Level

Si Chen 1 2Xiao-Ting Lu 1 2Tong-Tong He 1

Abstract

Scope: The muscle loss during aging results from the blunt of protein synthesis and poses threat to the elderly health. This study aimed to investigate whether betaine affects muscle loss by improving protein synthesis.

Methods and results: Male C57BL/6J mice were raised from aged 12 mon or 15 mon. Mice were fed with AIN-93M diet without or with 2% w/v betaine in distilled water as control group (Con) or betaine intervention group (Bet) respectively. Betaine supplementation to mice demonstrated better body composition, grip strength and motor function. Muscle morphology, upregulated expression of myogenic regulate factors (MRFs), and elevated myosin heavy chain (MyHC) also improved in Bet group. Betaine promoted muscle protein synthesis (MPS) via tethering mTORC1 on the lysosomal membrane thereby activating mTORC1 signaling. All these effects aforementioned were time-dependent (P < 0.05). UPLC results found betaine increased S-adenosyl-L-methionine (SAM) via methionine cycle. SAM sensor – Samtor – overexpression in C2C12 cells could displace mTORC1 from lysosome thereby inhibited the mTORC1 signaling. Addition of betaine attenuated this inhibition by increasing SAM level and then disrupting interaction of Samtor complex.

Conclusions: These observations indicated betaine could promisingly promote protein synthesis to delay age-related muscle loss.