Multiomics analyses decipher intricate changes in the cellular and metabolic landscape of steatotic livers upon dietary restriction and sleeve gastrectomy.
Document Type
Article
Publication Date
1-1-2024
Original Citation
Chen S,
Zeng Q,
Cai X,
Xue J,
Yin G,
Song P,
Tang L,
Klein C,
Tacke F,
Guillot A,
Liu H.
Multiomics analyses decipher intricate changes in the cellular and metabolic landscape of steatotic livers upon dietary restriction and sleeve gastrectomy. Int J Biol Sci. 2024;20(11):4438-57.
Keywords
JMG, Animals, Rats, Male, Gastrectomy, Fatty Liver, Humans, Liver, Diet, High-Fat, Rats, Sprague-Dawley, Metabolomics, Caloric Restriction, Multiomics
JAX Source
Int J Biol Sci. 2024;20(11):4438-57.
ISSN
1449-2288
PMID
39247824
DOI
https://doi.org/10.7150/ijbs.98362
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic, progressive liver disease that encompasses a spectrum of steatosis, steatohepatitis (or MASH), and fibrosis. Evidence suggests that dietary restriction (DR) and sleeve gastrectomy (SG) can lead to remission of hepatic steatosis and inflammation through weight loss, but it is unclear whether these procedures induce distinct metabolic or immunological changes in MASLD livers. This study aims to elucidate the intricate hepatic changes following DR, SG or sham surgery in rats fed a high-fat diet as a model of obesity-related MASLD, in comparison to a clinical cohort of patients undergoing SG. Single-cell and single-nuclei transcriptome analysis, spatial metabolomics, and immunohistochemistry revealed the liver landscape, while circulating biomarkers were measured in serum samples. Artificial intelligence (AI)-assisted image analysis characterized the spatial distribution of hepatocytes, myeloid cells and lymphocytes. In patients and experimental MASLD rats, SG improved body mass index, circulating liver injury biomarkers and triglyceride levels. Both DR and SG attenuated liver steatosis and fibrosis in rats. Metabolism-related genes (