n - 3 polyunsaturated fatty acids mediate hyodeoxycholic acid-FXR signaling to ameliorate metabolic dysfunction-associated fatty liver disease
Abstract
Accumulating evidence has shown that n - 3 polyunsaturated fatty acids (PUFA) intervention contributes to ameliorating metabolic dysfunction-associated fatty liver disease (MAFLD); however, the underlying mechanism through which n - 3 PUFA alleviate MAFLD remains elusive. Critical gut microbiota-modified metabolites and host targets have been implicated in the initiation and development of MAFLD. Here, a case-control study was performed which indicated that gut microbiota-modified bile acids, notably serum hydeoxycholic acid (HDCA) species, were significantly lower in MAFLD subjects compared with the healthy controls and were negatively associated with n - 3 PUFA proportions in red blood phospholipids, suggesting a link between n - 3 PUFA, HDCA and MAFLD. The causality was further confirmed by a double-blind, randomized placebo-controlled trial which showed that n - 3 PUFA supplementation significantly increased serum HDCA concentrations in MAFLD subjects in comparison with the control group. The MAFLD mouse model showed that administration of n - 3 PUFA mediated hepatic peroxisome proliferator-activated receptor alpha signaling to upregulate oxysterol 7α-hydroxylase (CYP7B1)-centered alternative bile acids synthetic pathway, contributing to increased HDCA concentrations. Administering HDCA to high-fat diet (HFD)-fed mice demonstrated that HDCA acts as an intestinal farnesoid X receptor (FXR) antagonist that decreased intestinal and hepatic ceramide accumulation, thereby…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
Read the paper
Related studies
- eggNOG 5.0: a hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses
- Online Survival Analysis Software to Assess the Prognostic Value of Biomarkers Using Transcriptomic Data in Non-Small-Cell Lung Cancer
- OptiType: precision HLA typing from next-generation sequencing data
- Nicotinic Cholinergic System and COVID-19: In Silico Identification of an Interaction between SARS-CoV-2 and Nicotinic Receptors with Potential Therapeutic Targeting Implications
- Saccharomyces cerevisiae cells have three Omega class glutathione S-transferases acting as 1-Cys thiol transferases
- Hemolysis at low blood flow rates: in-vitro and in-silico evaluation of a centrifugal blood pump
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.