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High-fat diet increases circulating palmitic acid produced by gut Bacteroides thetaiotaomicron to promote thrombosis

ABSTRACT:

Circulating palmitic acid (PA) is generally considered to be provided from diets and endogenous synthesis, and is adversely correlated with cardiovascular disease (CVD). It is unknown, however, if gut microbiota modulates circulating PA and potentiate CVD risk. Here we demonstrate that in CVD patients, elevated circulating PA is accompanied with hypercoagulability and high gut Bacteroides thetaiotaomicron (BT) abundance. PA promotes coagulation by inhibiting a major endogenous anticoagulant activated-protein-C (APC) and enhancing platelet activation. Importantly, BT is capable of synthesizing PA, and high-fat diet amplifies gut BT colonization. Our findings show that BT transplantation elevates plasma PA and triggers hypercoagulation without alternating host lipogenesis. Hesperidin, a dietary flavonoid, inhibits PA-APC interaction to prevent hypercoagulation induced by PA or BT transplantation. Collectively, we reveal the promotion of high-fat diet on gut BT colonization that elevates circulating PA and CVD, suggesting an approach controlling CVD by targeting PA and BT.

INSTRUMENT(S): Liquid Chromatography MS - - - Gas Chromatography MS - positive

PROVIDER: MTBLS12618 | MetaboLights | 2025-06-20

REPOSITORIES: MetaboLights

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			Action	DRS
	a_MTBLS12618_GC-MS_positive__metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS12618_GC-MS_positive__metabolite_profiling_v2_maf.tsv	Tabular
	s_MTBLS12618.txt	Txt

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