title: β-Cryptoxanthin alleviates diet-induced nonalcoholic steatohepatitis by suppressing inflammatory gene expression in mice.
abstract: 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% β-cryptoxanthin to C56BL/6J mice for 12 weeks. After feeding, β-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 β-cryptoxanthin histochemically reduced steatosis, it was more effective in inhibiting inflammatory gene expression change in NASH. β-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 β-cryptoxanthin. β-Cryptoxanthin suppressed the expression of lipopolysaccharide (LPS)-inducible and/or TNFα-inducible genes in NASH. Increased levels of the oxidative stress marker thiobarbituric acid reactive substances (TBARS) were reduced by β-cryptoxanthin in NASH. Thus, β-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.
authors.affiliation: National Food Research Institute, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
authors.forename: Masuko
authors.initials: M
authors.lastname: Kobori
authors.affiliation: Department of Cell Metabolism and Nutrition, Brain/Liver Interface Medicine Research Center, Kanazawa University, Kanazawa, Ishikawa, Japan; Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
authors.forename: Yinhua
authors.initials: Y
authors.lastname: Ni
authors.affiliation: National Food Research Institute, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: National Food Research Institute, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Watanabe
authors.affiliation: Citrus Research Division, NARO Institute of Fruit Tree Science, National Agriculture and Food Research Organization, Shimizu, Shizuoka, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Sugiura
authors.affiliation: Grape and Persimmon Research Division, NARO Institute of Fruit Tree Science, National Agriculture and Food Research Organization, Higashi-hiroshima, Hiroshima, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: Department of Cell Metabolism and Nutrition, Brain/Liver Interface Medicine Research Center, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nagashimada
authors.affiliation: Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: National Food Research Institute, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Naito
authors.affiliation: Department of Cell Metabolism and Nutrition, Brain/Liver Interface Medicine Research Center, Kanazawa University, Kanazawa, Ishikawa, Japan; Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan.
authors.forename: Tsuguhito
authors.initials: T
authors.lastname: Ota
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis*; D002784:Cholesterol / Q000009:adverse effects* / Q000494:pharmacology; D065366:Cryptoxanthins / Q000494:pharmacology*; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D007333:Insulin Resistance; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D065626:Non-alcoholic Fatty Liver Disease / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
chemical_list: D000943:Antigens, Differentiation; D065366:Cryptoxanthins; D004041:Dietary Fats; D002784:Cholesterol