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Dietary restriction of lysine reduces pediatric obesity through enhancing Parabacteroides goldsteinii-produced 1,4-Methylimidazoleacetic acid

ABSTRACT:

The influence of amino acid restriction on obesity may be related to the gut microbiome, but the role and mechanism of lysine restriction (LR) on pediatric obesity is largely undefined. Here, we found plasma lysine levels were significantly higher in obese patients than healthy controls of children, and LR reduced obesity in young animal models. Interestingly, the anti-obesity effect of LR was achieved via gut microbiota. Moreover, we identified that Parabacteroides goldsteinii (P.goldsteinii) was the key species substantially affected obesity, and supplementing mice with this bacteria profoundly reduced obesity. By using metabolomics, our results showed P. goldsteinii alleviated obesity through its produced metabolite 1,4-methylimidazoleacetic acid (MIAA). Our mechanistic data further reveled that MIAA supplementation increased the m6A modification levels of solute carrier family 2 member 4 (Slc2a4) mRNA by inhibiting the fat mass and obesity gene (FTO)-mediated reading protein YTH N6-methyladenosine RNA-binding protein C1 (YTHDC1), and thereby reducing the body weights. Overall, LR reduces paediatric obesity through P. goldsteinii-produced MIAA via its regulation of the FTO–YTHDC1–SLC2A4-axis.

INSTRUMENT(S): Liquid Chromatography MS - positive - HILIC, Liquid Chromatography MS - negative - HILIC

PROVIDER: MTBLS13011 | MetaboLights | 2025-09-18

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS13011_LC-MS_negative_hilic_metabolite_profiling.txt	Txt
	a_MTBLS13011_LC-MS_positive_hilic_metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS13011_LC-MS_negative_hilic_metabolite_profiling_v2_maf.tsv	Tabular
	m_MTBLS13011_LC-MS_positive_hilic_metabolite_profiling_v2_maf.tsv	Tabular

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