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M-NM-2-Cryptoxanthin suppresses inflammatory gene expression in diet-induced nonalcoholic steatohepatitis in mice


ABSTRACT: To evaluate the effect of M-NM-2-cryptoxanthin on diet-induced NASH, we fed a high-cholesterol and high-fat diet (CL diet) with or without 0.003% M-NM-2-cryptoxanthin to C56BL/6J mice for 12 weeks. After feeding, M-NM-2-cryptoxanthin attenuated fat accumulation, increases in Kupffer and activated stellate cells, and fibrosis in CL diet-induced NASH in the mice. Comprehensive gene expression analysis showed that although M-NM-2-cryptoxanthin histochemically reduced steatosis, it was more effective in inhibiting inflammatory gene expression change in NASH. M-NM-2-Cryptoxanthin reduced the alteration of expression of genes associated with cell death, inflammatory responses, infiltration and activation of macrophages and other leukocytes, quantity of T cells, and free radical scavenging. However, it showed little effect on the expression of genes related to cholesterol and other lipid metabolism. The expression of markers of M1 and M2 macrophages, T helper cells, and cytotoxic T cells was significantly induced in NASH and reduced by M-NM-2-cryptoxanthin. M-NM-2-Cryptoxanthin suppressed the expression of lipopolysaccharide (LPS)-inducible and/or TNFM-NM-1-inducible genes and the antioxidant enzyme glutathione peroxidase 1 in NASH. Thus, M-NM-2-cryptoxanthin suppresses inflammation and the resulting fibrosis probably by primarily suppressing the increase and activation of macrophages and other immune cells. Reducing oxidative stress is likely to be a major mechanism of inflammation and injury suppression in the livers of mice with NASH. Eight-week old male C57BL/6J mice were fed for 12 weeks on a CRF-1 standard chow (control), a high-cholesterol and high-fat diet (CL diet; 38.23% CRF-1, 60% cocoa butter, 1.25% cholesterol, 0.5% sodium cholate) or a CL diet containing 0.003% M-NM-2-cryptoxanthin.

ORGANISM(S): Mus musculus

SUBMITTER: Masuko Kobori 

PROVIDER: E-GEOD-51432 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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β-Cryptoxanthin alleviates diet-induced nonalcoholic steatohepatitis by suppressing inflammatory gene expression in mice.

Kobori Masuko M   Ni Yinhua Y   Takahashi Yumiko Y   Watanabe Natsumi N   Sugiura Minoru M   Ogawa Kazunori K   Nagashimada Mayumi M   Kaneko Shuichi S   Naito Shigehiro S   Ota Tsuguhito T  

PloS one 20140523 5


Recent nutritional epidemiological surveys showed that serum β-cryptoxanthin inversely associates with the risks for insulin resistance and liver dysfunction. Consumption of β-cryptoxanthin possibly prevents nonalcoholic steatohepatitis (NASH), which is suggested to be caused by insulin resistance and oxidative stress from nonalcoholic fatty liver disease. To evaluate the effect of β-cryptoxanthin on diet-induced NASH, we fed a high-cholesterol and high-fat diet (CL diet) with or without 0.003%  ...[more]

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