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 wildtype (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.
| Original language | English |
|---|---|
| Article number | e0152549 |
| Journal | PloS one |
| Volume | 11 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 2016 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
- General
Cite this
Overexpression of peroxiredoxin 4 affects intestinal function in a dietary mouse model of nonalcoholic fatty liver disease. / Nawata, Aya; Noguchi, Hirotsugu; Mazaki, Yuichi; Kurahashi, Toshihiro; Izumi, Hiroto; Wang, Ke Yong; Guo, Xin; Uramoto, Hidetaka; Kohno, Kimitoshi; Taniguchi, Hatsumi; Tanaka, Yoshiya; Fujii, Junichi; Sasaguri, Yasuyuki; Tanimoto, Akihide; Nakayama, Toshiyuki; Yamada, Sohsuke.
In: PloS one, Vol. 11, No. 4, e0152549, 04.2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Overexpression of peroxiredoxin 4 affects intestinal function in a dietary mouse model of nonalcoholic fatty liver disease
AU - Nawata, Aya
AU - Noguchi, Hirotsugu
AU - Mazaki, Yuichi
AU - Kurahashi, Toshihiro
AU - Izumi, Hiroto
AU - Wang, Ke Yong
AU - Guo, Xin
AU - Uramoto, Hidetaka
AU - Kohno, Kimitoshi
AU - Taniguchi, Hatsumi
AU - Tanaka, Yoshiya
AU - Fujii, Junichi
AU - Sasaguri, Yasuyuki
AU - Tanimoto, Akihide
AU - Nakayama, Toshiyuki
AU - Yamada, Sohsuke
PY - 2016/4
Y1 - 2016/4
N2 - 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 wildtype (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.
AB - 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 wildtype (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.
UR - http://www.scopus.com/inward/record.url?scp=84962910422&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84962910422&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0152549
DO - 10.1371/journal.pone.0152549
M3 - Article
C2 - 27035833
AN - SCOPUS:84962910422
VL - 11
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 4
M1 - e0152549
ER -