Metabolomic, Lipidomic, and Enterohormone Changes in the Progression from MASLD to MASH
Rivas, J. A.; Murphy, A. C.; Prasad, P.; Goitom, S. S.; Romero, A. S.; Maes, B. B.; Akepati, P. R.; Garcia, M. A.; Lauer, F. T.; Gullapalli, R. R.; Gonzales, K. M.; Gross, J. M.; Pu, J.; Leng, S.; In, J. G.; McReynolds, M. R.; Castillo, E. F.
Show abstract
Background & AimsMetabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic Dysfunction-Associated Steatohepatitis (MASH) represent progressive stages of liver disease, with distinct metabolic and cellular alterations. This study investigates the progression from MASLD to MASH through metabolomics, lipidomics, and assessment of hormones. MethodsMale C57BL/6NTac mice were fed a high-fat diet for 16 weeks to induce MASLD and for 29 weeks to develop MASH. Aged-matched controls on a normal diet were used for comparison. Histology confirmed the progression of MASLD to MASH. We performed metabolomic and lipidomic profiling of liver, colon, and stool samples to identify metabolic and lipid alterations. Plasma enteroendocrine hormones and cytokines were quantified. Immunofluorescence was performed to assess enteroendocrine cells changes in the colon and the association of serotonin (5-HT) with fibronectin in the liver. ResultsMetabolomic and lipidomic analysis revealed significant alterations at different stages of the disease. Specifically, cholic acid was increased across the liver, colon, and stool in both MASLD and MASH mice compared to controls. Compared to the control group, MASLD mice exhibited an increase in enteroendocrine hormones, GLP-1, GIP, and PYY, whereas no changes were observed in MASH mice. Comparing MASLD to MASH livers, we found hepatic 5-HT levels were increased in MASH mice compared to MASLD mice. The MASH liver also exhibited a colocalization between fibronectin and 5-HT, suggesting a potential role of 5-HT in liver fibrosis. ConclusionsOur study provides novel insights into the progressive metabolic and hormonal changes from MASLD to MASH. The increase in cholic acid and differential enteroendocrine hormone responses highlight the complex interactions between the gut and liver in metabolic liver diseases. These findings suggest that enteroendocrine hormones may play a role in the progression of MASLD to MASH as well as liver fibrosis, offering potential therapeutic avenues for targeting the gut-liver axis in metabolic liver diseases.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Hepatocyte Circadian Clocks Control Cholesterol Metabolism and Protect From Metabolic Dysfunction-Associated Steatohepatitis (MASH) 95%
- Gut dysbiosis protects against liver injury in autophagy deficient mice by FXR-FGF15 feedback signaling 94%
- CD73 maintains hepatocyte metabolic integrity and mouse liver homeostasis in a sex-dependentmanner 94%
Similar papers in this journal
- Lysine tRNA fragments and miR-194-5p co-regulate hepatic steatosis via beta-Klotho and Perilipin 2 96%
- Loss of Carnitine Palmitoyltransferase 1a Reduces Docosahexaenoic Acid-Containing Phospholipids and Drives Sexually Dimorphic Liver Disease in Mice 95%
- Differential cell type-specific function of the aryl hydrocarbon receptor and its repressor in diet-induced obesity and fibrosis 95%
Similar papers in this journal
- Gestational insulin resistance is mediated by the gut microbiome-indoleamine 2,3-dioxygenase axis 95%
- iPSC-derived hepatocytes from patients with nonalcoholic fatty liver disease display a disease-specific gene expression profile 93%
- Systemic identification of functionally conserved lncRNA metabolic regulators in human and mouse livers 93%
Similar papers in this journal
- Complement 3a Receptor 1 on Macrophages and Kupffer cells is not required for the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease 96%
- Sex differences in bile acid homeostasis and excretion underlie the disparity in liver cancer incidence between males and females. 96%
- Oral supplementation of gut microbial metabolite indole-3-acetate alleviates diet-induced steatosis and inflammation in mice 96%
Similar papers in this journal
- Lysates of Methylococcus capsulatus Bath induce a lean-like microbiota, intestinal FoxP3+RORγt+IL-17+ Tregs and improve metabolism 97%
- Autocrine IL11 cis-signaling in hepatocytes is an initiating nexus between lipotoxicity and non-alcoholic steatohepatitis 96%
- Liver-innervating vagal sensory neurons play an indispensable role in the development of hepatic steatosis and anxiety-like behavior in mice fed a high-fat diet. 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.