Editorial Type:
Article Category: Research Article
 | 
Online Publication Date: 14 May 2025

Evaluation of Serum L-FABP as a Biomarker and Hepatoprotective Effect of L-FABP Using Wild-Type and Human L-FABP Chromosome Transgenic Mice

MS,
MS,
PhD,
MS,
PhD,
MD, PhD,
PhD, and
DVM, PhD
Page Range: 1 – 10
DOI: 10.30802/AALAS-JAALAS-25-003
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Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are the major prevalent liver diseases and growing public health problems worldwide. Because MASLD/MASH is known as a risk for progression to cirrhosis and development of hepatocellular carcinoma, therapeutic approaches and biomarkers that reflect the presence and progression of the disease are needed. In recent years, the usefulness of serum L-FABP levels has been reported for monitoring of hepatocellular damage in various liver diseases including MASLD/MASH in humans. Furthermore, it is reported that hepatic L-FABP is a potential therapeutic target. The purpose of this study was to validate the usefulness of serum L-FABP as a liver damage biomarker in the mouse model of MASLD/MASH and to evaluate the function of L-FABP in the pathogenesis of MASLD/MASH. First, we evaluated the changes in serum L-FABP as a liver damage biomarker using a mouse model of MASLD/MASH fed a choline-deficient, methionine-lowered, amino acid-defined, high-fat diet. The results demonstrated that serum L-FABP levels in the MASLD/MASH model continuously increased with the progression of steatosis and correlated with histopathologic changes. Serum L-FABP may be a useful biomarker for liver disease with respect to translational research bridging between animal models and human clinical research. Further, we showed that in human L-FABP chromosomal transgenic mice L-FABP had a suppressive effect on the gene expression associated with oxidative stress, fibrosis, and inflammation in the MASLD/MASH model. L-FABP is not only a biomarker in the blood but also has the functional aspect of hepatoprotection against MASLD/MASH.

Copyright: © American Association for Laboratory Animal Science
<bold>Figure 1.</bold>
Figure 1.

(A) Histopathological changes in liver tissues of WT and hL-FABP Tg mice after CDAA-HFD or SD feeding for 26 wk. (SR, Sirius red staining; HE, hematoxylin and eosin staining). Steatosis, fibrosis, hepatocyte hypertrophy, and inflammatory cell infiltration were observed in both WT and hL-FABP Tg mice after CDAA-HFD feeding. Bar = 100 μm. (B) Changes in food consumption in CDAA-HFD or SD fed mice (w, week).


<bold>Figure 2.</bold>
Figure 2.

Changes in serum L-FABP levels: (A) WT-serum mouse L-FABP; (B) hL-FABP Tg-serum mouse L-FABP; (C) hL-FABP Tg-serum human L-FABP. Data of CDAA-HFD fed mice are shown in the gray boxes, and data of SD fed mice are shown in the white boxes (W, week). Correlation of serum L-FABPs with MASLD activity score: (D) WT-serum mouse L-FABP; (E) hL-FABP Tg-serum mouse L-FABP; (F) hL-FABP Tg-serum human L-FABP. Lines in the figure indicate regression lines and the CI. *, P ≤ 0.05; **, P ≤ 0.01.


<bold>Figure 3.</bold>
Figure 3.

Correlation of serum L-FABPs with fatty change score, hepatocyte hypertrophy score, fibrosis score, and inflammatory cell infiltration: (A–D) WT-serum mouse L-FABP; (E–H) hL-FABP Tg-serum mouse L-FABP; (I–L) hL-FABP Tg-serum human L-FABP. Lines in the figure indicate regression lines and the CI.


<bold>Figure 4.</bold>
Figure 4.

Immunohistological staining of liver tissues at 26 wk using anti-human L-FABP antibody in CDAA-HFD or SD fed hL-FABP Tg mice. Bar = 100 μm.


<bold>Figure 5.</bold>
Figure 5.

(A) Changes in urinary human L-FABP in CDAA-HFD- or SD-fed hL-FABP Tg mice. (B) Histopathological changes in kidney tissues of hL-FABP Tg mice after CDAA-HFD or SD feeding for 26 wk (H&E staining). Bar = 100 μm.


<bold>Figure 6.</bold>
Figure 6.

Changes in ALT and AST in serum in CDAA-HFD- or SD-fed WT and hL-FABP Tg mice: (A) ALT; (B) AST. Changes in gene expression in the liver in CDAA-HFD- or SD-fed WT and hL-FABP Tg mice: (C) p67 phox; (D) TGF-β; (E) TNF-α; (F) MCP-1; (G) collagen-1a. Data of hL-FABP Tg mice are shown in the gray boxes, and data of WT mice are shown in the white boxes. *, P ≤ 0.05 WT compared with hL-FABP Tg mice. †, P ≤ 0.05, compared with SD fed mice. §, P ≤ 0.05, compared with the values at 2 wk for each strain.


Contributor Notes

Corresponding author. Email: keiichi-ohata@marianna-u.ac.jp
These authors contributed equally to this study.
Received: 07 Jan 2025
Accepted: 15 Apr 2025
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