Tier 3 — preclinical

Glycine-based treatment ameliorates NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome

Rom O, Liu Y, Liu Z, Zhao Y, Wu J, Ghrayeb A, Villacorta L, Fan Y, Chang L, Wang L, Liu C, Yang D, Song J, Rech JC, Guo Y, Wang H, Zhao G, Liang W, Koike Y, Lu H, Koike T, Hayek T, Pennathur S, Xi C, Wen B, Sun D, Garcia-Barrio MT, Aviram M, Gottlieb E, Mor I, Liu W, Zhang J, Chen YE
Science translational medicine 2020 12(572):eaaz2841

Bibliography

PubMed
PMID 33268508
PubMed Central
PMC7982985
DOI
10.1126/scitranslmed.aaz2841
Funding
Indexed support: National Heart, Lung, and Blood Institute; NIDDK NIH HHS; Michigan Center for Therapeutic Innovation; NHLBI NIH HHS; Michigan-Israel partnership for research and education; National Institute of Diabetes and Digestive and Kidney Diseases; American Heart Association; NCI NIH HHS. See the publication for grant and funder details.
Competing interests
The accessible abstract does not establish the authors' competing interests; absence of a statement is not evidence of no conflicts.

Study snapshot

DesignHuman association/genetic analyses with animal experiments
ModelHuman/mouse liver transcriptomics and mouse steatohepatitis models
SampleHuman and mouse transcriptomics plus multiple mouse intervention cohorts
InterventionGlycine-availability perturbation and DT-109 tripeptide treatment
DurationModel-specific experimental periods
EndpointsFatty-acid oxidation; Steatohepatitis; Glutathione; Gut microbiome

What the study showed, in plain terms

The study linked glycine metabolism with fatty-liver biology and found benefits from DT-109 in mice. A glycine-containing therapeutic tripeptide is not interchangeable with isolated glycine powder.

Key findings

  • Glycine-limiting genetic or dietary changes worsened experimental liver phenotypes.
  • DT-109 improved selected metabolic, inflammatory and fibrosis measures in mice.

What this study can and cannot tell us

The principal treatment was a distinct tripeptide, not a human glycine supplement trial.

Experimental steatohepatitis findings do not establish treatment of human MASLD.

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Editorial review

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction