Intrahepatic fatty acids composition as a biomarker of NAFLD progression from steatosis to NASH by using¹H-MRS

Abstract

Our results suggest that it would be possible to detect the progression of simple steatosis to NASH using 1H-MRS.

Impact of the Co-Administration of N-3 Fatty Acids and Olive Oil Components in Preclinical Nonalcoholic Fatty Liver Disease Models: A Mechanistic View

“…Importantly, a recent report identified 25 genes that are dysregulated during steatosis progression to NASH, including the significant loss of those encoding for PPAR-α and PGC-1α, which drastically disturb mitochondrial function [50]. Furthermore, progression of steatosis to NASH decreases the content of liver LCPUFA by 59%, 78%, and 89% compared with control values in mice subjected to a Western diet (40% energy as fat) for 4, 10, and 24 weeks, respectively [51]. Besides supporting liver FAO, n-3 LCPUFA promote the decline of hepatic de novo lipogenesis through at least three mechanisms of action, namely, (i) diminution of the nuclear availability of the lipogenic transcription factor sterol regulatory element binding protein-1c (SREBP-1c) via AMPK-mediated serine-365 phosphorylation of nascent SREBP-1c, resulting in inhibition of the intramembrane proteolysis of the nascent SREBP-1c ( Figure 2; [52]); (ii) DHA-dependent downregulation of the expression of SREBP-1c and target lipogenic enzymes through interaction with G-protein-coupled receptor 40 (GPR40) [53]; and (iii) n-3 LCPUFA-dependent repression of the citrate carrier (CIC) expression secondary to SREBP-1c downregulation, thus decreasing the transport of mitochondrial acetyl-CoA units as citrate outside mitochondria for FA synthesis ( Figure 2) [49].…”

Characterization of hepatic fatty acids using magnetic resonance spectroscopy for the assessment of treatment response to metformin in an eNOS−/− mouse model of metabolic nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

“…However, no significant changes were detected in structural lipids. Our findings identify a specific cluster in the PCA of the 1 H‐NMR lipid spectra in eNOS −/− mice during NAFLD progression compared with WT mice that could provide new hypotheses for the metabolic changes in the progression of this disease, and highlights the potential of 1 H‐MRS as a noninvasive tool for diagnosis and follow‐up of patients, as other studies have suggested 73,74 . However, there is evidence that the distribution of liver damage is not homogeneous throughout the liver 75 .…”

“…Our findings identify a specific cluster in the PCA of the 1 H-NMR lipid spectra in eNOS À/À mice during NAFLD progression compared with WT mice that could provide new hypotheses for the metabolic changes in the progression of this disease, and highlights the potential of 1 H-MRS as a noninvasive tool for diagnosis and follow-up of patients, as other studies have suggested. 73,74 However, there is evidence that the distribution of liver damage is not homogeneous throughout the liver. 75 However, in this study we used large voxels that practically covered the entire right or left lobe of the animal, thus it was not possible to identify differences between the different liver segments.…”

Pathogenesis of MASLD and MASH – role of insulin resistance and lipotoxicity

“…Other studies have attempted to correlate MASLD progression with toxic lipid intermediates, such as DAGs, by leveraging gas chromatography with mass spectrometry and magnetic resonance spectroscopy to determine intracellular fatty acid composition changes as MASLD progresses from simple steatosis to steatohepatitis (MASH). As the disease progressed, this study found that the amount of PUFA (polyunsaturated fatty acids) decreased, MUFA (monounsaturated fatty acids) increased and SFA (saturated fatty acids) remained the same 96 . The extent to which this becomes clinically relevant and surpasses the value of merely measuring triglyceride content via MRI‐PDFF as a surrogate is yet to be determined.…”

“…As the disease progressed, this study found that the amount of PUFA (polyunsaturated fatty acids) decreased, MUFA (monounsaturated fatty acids) increased and SFA (saturated fatty acids) remained the same. 96 The extent to which this becomes clinically relevant and surpasses the value of merely measuring triglyceride content via MRI-PDFF as a surrogate is yet to be determined. Clinical trial data suggest that MRI-PDFF reductions correlate with MASH resolution, contingent upon the disease's mechanism of action.…”