首页|Essentiality of SLC7A11-mediated nonessential amino acids in MASLD

Essentiality of SLC7A11-mediated nonessential amino acids in MASLD

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Metabolic dysfunction-associated steatotic liver disease(MASLD)remains a rapidly growing global health burden.Here,we report that the nonessential amino acid(NEAA)transporter SLC7A11 plays a key role in MASLD.In patients with MASLD,we found high expression levels of SLC7A11 that were correlated directly with clinical grade.Using both loss-of-function and gain-of-function genetic models,we found that Slc7al 1 deficiency accelerated MASLD progression via classic cystine/cysteine deficiency-induced ferroptosis,while serine deficiency and a resulting impairment in de novo cysteine production were attributed to ferroptosis-induced MASLD progression in mice overexpressing hepatic Slc7a11.Consistent with these findings,we found that both serine supplementation and blocking ferroptosis significantly alleviated MASLD,and the serum serine/glutamate ratio was significantly lower in these pre-clinical disease models,suggesting that it might serve as a prognostic biomarker for MASLD in patients.These findings indicate that defects in NEAA metabolism are involved in the progression of MASLD and that serine deficiency-triggered ferroptosis may provide a therapeutic target for its treatment.

SLC7A11MASLDSerine synthesisFerroptosisNAFLD

Jie Shen、Enjun Xie、Shuying Shen、Zijun Song、Xiaopeng Li、Fudi Wang、Junxia Min

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The First Affiliated Hospital,Institute of Translational Medicine,Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism,Zhejiang University School of Medicine,Hangzhou 310058,China

The Second Affiliated Hospital,School of Public Health,State Key Laboratory of Experimental Hematology,Zhejiang University School of Medicine,Hangzhou 310058,China

School of Public Health,School of Basic Medical Sciences,The First Affiliated Hospital,Hengyang Medical School,University of South China,Hengyang 4

School of Public Health,School of Basic Medical Sciences,The First Affiliated Hospital,Hengyang Medical School,University of South China,Hengyang 421001,China

School of Public Health,School of Basic Medical Sciences,The First Affiliated Hospital,Xinxiang Medical University,Xinxiang 453003,China

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2024

10.1016/j.scib.2024.09.019

科学通报(英文版)
中国科学院

科学通报(英文版)

CSTPCD
ISSN：1001-6538
年,卷(期)：2024.69(23)