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, 6 (3), 381-7

Involvement of Nuclear Factor Kappa B in High-Fat Diet-Related Pancreatic Fibrosis in Rats

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Involvement of Nuclear Factor Kappa B in High-Fat Diet-Related Pancreatic Fibrosis in Rats

Ming-Xian Yan et al. Gut Liver.

Abstract

Background/aims: High-fat diets contribute to pancreatic fibrogenesis, but the pathogenesis remains unclear. This study investigated the role of nuclear factor kappa B (NF-κB) in high-fat diet-induced pancreatic fibrosis in rats.

Methods: Male Wistar rats were fed a high-fat diet or standard normal chow for 20 weeks. Pancreatic fibrosis was determined by Sirius red staining. Immunohistochemical staining, reverse transcription-polymerase chain reaction and Western blotting were used to identify NF-κB-associated genes or protein expressions.

Results: Inflammation, fat deposition, pancreatic stellate cell activation and fibrosis were observed in the pancreases of the high-fat diet group. NF-κB subunit p65 (NF-κB/p65) expression was localized to the nucleus, and intercellular adhesion molecule 1 (ICAM-1) was over-expressed. Pancreatic gene expression levels of NF-κB/p65, ICAM-1 and tumor necrosis factor α were all elevated significantly in rats fed a high-fat diet compared with control rats. Western blotting also revealed significantly increased levels of ICAM-1 and nuclear NF-κB/p65 in rats fed high-fat diets comparison with control rats.

Conclusions: NF-κB is involved in high-fat diet-related pancreatic fibrosis.

Keywords: High-fat diet; Intercellular adhesion molecule 1; NF-kappa B; Pancreatic fibrosis; Tumor necrosis factor-alpha.

Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1
Fig. 1
(A, B) Hematoxylin-eosin (H&E stain, ×200) and (C, D) Sirius red staining (×200) in pancreatic samples. The collagen fibrils appear red, and the non-fibrotic areas appear blue after Sirius red staining. The stained sections display none of the obvious histopathological changes observed in the control group (A, C), but fat deposition in acinar cells (cytoplasmic vacuolization), lymphocyte infiltration and collagen deposition were observed in the high-fat diet group (B, D), indicating the presence of fibrogenesis in the pancreas after prolonged ingestion of a high-fat diet. Control, n=10; High-fat, n=12.
Fig. 2
Fig. 2
Immunohistochemical staining for nuclear factor kappa B p65 (NF-κB/p65), intercellular adhesion molecule 1 (ICAM-1), and α smooth muscle actin (α-SMA) (×400) and the corresponding statistical analysis. (A) Representative immunohistochemistry for NF-κB/p65 (a, b), ICAM-1 (c, d) and α-SMA (e, f) (control, a, c, e; high-fat, b, d, f). For NF-κB/p65 staining, cells with stained cytoplasm and a stained nucleus (brown) were considered positive. (B, C) The corresponding statistical analysis. The average number of NF-κB/p65- or ICAM-1-positive stained (brown) cells per high power field is reported. Areas staining positive for α-SMA are expressed as percentages of the total area. Data are presented as means±SD. Control, n=10; High-fat, n=12. *p<0.001, control versus high-fat diet group.
Fig. 3
Fig. 3
Gene expression in pancreatic samples. (A) Reverse transcription-polymerase chain reaction (RT-PCR) results for nuclear factor kappa B p65 (NF-κB/p65) (a), intercellular adhesion molecule 1 (ICAM-1) (b), tumor necrosis factor α (TNF-α) (c), and β-actin (d). Representative RT-PCR results are displayed. (B) The relative intensity of PCR production bands was analyzed using ImageJ software (National Institutes of Health). Data are expressed as the ratio of each mRNA to the corresponding β-actin mRNA. Data are presented as means±SD. Control, n=10; High-fat, n=12. *p<0.001, control (1) versus the high-fat (2) diet group.
Fig. 4
Fig. 4
Protein expression in pancreatic samples. (A) Western blots displaying the expression of intra-nuclear protein nuclear factor kappa B (NF-κB)/p65 and cytosolic protein intercellular adhesion molecule 1 (ICAM-1). A representative image from three experiments is displayed. (B) The relative intensity of the Western blot bands was analyzed using ImageJ software. The data are expressed as percentages of the control values. Data are presented as means±SD. Control, n=10; High-fat, n=12. *p<0.001, control versus high-fat diet.

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