Overexpression of Peroxiredoxin 4 Affects Intestinal Function in a Dietary Mouse Model of Nonalcoholic Fatty Liver Disease.

Abstract

BACKGROUND:

Accumulating evidence has shown that methionine- and choline-deficient high fat (MCD+HF) diet induces the development of nonalcoholic fatty liver disease (NAFLD), in which elevated reactive oxygen species play a crucial role. We have reported that peroxiredoxin 4 (PRDX4), a unique secretory member of the PRDX antioxidant family, protects against NAFLD progression. However, the detailed mechanism and potential effects on the intestinal function still remain unclear.

METHODS & RESULTS:

Two weeks after feeding mice a MCD+HF diet, the livers of human PRDX4 transgenic (Tg) mice exhibited significant suppression in the development of NAFLD compared with wild-type (WT) mice. The serum thiobarbituric acid reactive substances levels were significantly lower in Tg mice. In contrast, the Tg small intestine with PRDX4 overexpression showed more suppressed shortening of total length and villi height, and more accumulation of lipid in the jejunum, along with lower levels of dihydroethidium binding. The enterocytes exhibited fewer apoptotic but more proliferating cells, and inflammation was reduced in the mucosa. Furthermore, the small intestine of Tg mice had significantly higher expression of cholesterol absorption-regulatory factors, including liver X receptor-α, but lower expression of microsomal triglyceride-transfer protein.

CONCLUSION:

Our present data provide the first evidence of the beneficial effects of PRDX4 on intestinal function in the reduction of the severity of NAFLD, by ameliorating oxidative stress-induced local and systemic injury. We can suggest that both liver and intestine are spared, to some degree, by the antioxidant properties of PRDX4.

• Authors: Aya Nawata, Hirotsugu Noguchi, Yuichi Mazaki, Toshihiro Kurahashi, Hiroto Izumi, Ke-Yong Wang, Xin Guo, Hidetaka Uramoto, Kimitoshi Kohno, Hatsumi Taniguchi, Yoshiya Tanaka, Junichi Fujii, Yasuyuki Sasaguri, Akihide Tanimoto, Toshiyuki Nakayama, Sohsuke Yamada
• Journal: PloS one (PLoS One) Vol. 11 Issue 4 Pg. e0152549 ( 2016) ISSN: 1932-6203 [Electronic] United States
• PMID: 27035833 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Ribosomal, 16S
• Peroxiredoxins

Topics

• Animals
• Disease Models, Animal
• Disease Progression
• Intestines (microbiology)
• Mice
• Mice, Transgenic
• Microbiota
• Non-alcoholic Fatty Liver Disease (metabolism, physiopathology)
• Peroxiredoxins (metabolism)
• RNA, Ribosomal, 16S (genetics)