title: Deficiency of dietary niacin impaired intestinal mucosal immune function via regulating intestinal NF-κB, Nrf2 and MLCK signaling pathways in young grass carp (Ctenopharyngodon idella).
abstract: This study investigated the effects of dietary niacin on intestinal mucosal immune and physical barrier, and relative mRNA levels of signaling molecules in the intestine of young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp (255.63 ± 0.41 g) were fed six diets containing graded levels of niacin (3.95, 14.92, 24.98, 35.03, 44.97 and 55.01 mg/kg diet) for 8 weeks. Results observed that niacin deficiency decreased lysozyme (LA) and acid phosphatase (ACP) activities, and complement 3 (C3) content in the intestine (P < 0.05), down-regulated mRNA levels of liver expressed antimicrobial peptide 2 (LEAP-2), hepcidin, interleukin 10, transforming growth factor β1 and inhibitor of κBα (IκBα) (P < 0.05), up-regulated tumor necrosis factor α, interleukin 1β, interferon γ2, interleukin 8, nuclear factor kappa B P65 (NF-κB P65), IκB kinase α (IKKα), IκB kinase β (IKKβ) and IκB kinase γ (IKKγ) in all intestinal segments of young grass carp (P < 0.05). In addition, niacin deficiency increased reactive oxygen species (ROS), malondialdehyde (MDA) and protein carbonyl (PC) contents, decreased glutathione content, and copper/zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferases (GST) and glutathione reductase (GR) activities in the intestine of young grass carp (P < 0.05). Additionally, niacin deficiency decreased mRNA levels of CuZnSOD, MnSOD, GPx, CAT, GST, GR, Claudin b, Claudin 3, Claudin c, Occludin, ZO-1, Claudin 15 and NF-E2-related factor 2 (Nrf2) (P < 0.05), and increased Claudin 12, Kelch-like ECH-associating protein 1a (Keap1a), myosin light-chain kinase (MLCK) and p38 mitogen-activated protein kinase (p38 MAPK) mRNA expression levels in the intestine of young grass carp (P < 0.05), while the mRNA level of Kelch-like ECH-associating protein 1b (Keap1b) did not change (P > 0.05). In conclusion, niacin deficiency decreased intestinal mucosal immune and intestinal physical function, as well as regulated mRNA levels of NF-κB P65, IκBα, IKKα, IKKβ, IKKγ, Nrf2, Keap1a, p38 MAPK and MLCK in the intestine of young grass carp. Based on the broken-line model analysis of intestinal lysozyme activity, the requirement of niacin for young grass carp (255.63 ± 0.41 g) were estimated to be 39.80 mg/kg diet.
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, Sichuan, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Agricultural University, Chengdu, 611130, Sichuan, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Feng
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, Sichuan, China.
authors.forename: Shun-Quan
authors.initials: SQ
authors.lastname: Li
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, Sichuan, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Agricultural University, Chengdu, 611130, Sichuan, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China.
authors.forename: Wei-Dan
authors.initials: WD
authors.lastname: Jiang
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, Sichuan, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Agricultural University, Chengdu, 611130, Sichuan, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, Sichuan, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Agricultural University, Chengdu, 611130, Sichuan, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, Sichuan, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Agricultural University, Chengdu, 611130, Sichuan, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Wu
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, Sichuan, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Agricultural University, Chengdu, 611130, Sichuan, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, Sichuan, China.
authors.forename: Sheng-Yao
authors.initials: SY
authors.lastname: Kuang
authors.affiliation: Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, Sichuan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Tang
authors.affiliation: Animal Nutrition Institute, Sichuan Academy of Animal Science, Chengdu, 610066, Sichuan, China.
authors.forename: Wu-Neng
authors.initials: WN
authors.lastname: Tang
authors.affiliation: Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.
authors.forename: Yong-An
authors.initials: YA
authors.lastname: Zhang
authors.affiliation: Animal Nutrition Institute, Sichuan Agricultural University, Sichuan, Chengdu, 611130, Sichuan, China; Fish Nutrition and Safety Production University Key Laboratory of Sichuan Agricultural University, Chengdu, 611130, Sichuan, China; Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Sichuan Agricultural University, Chengdu, 611130, Sichuan, China. Electronic address: xqzhouqq@tom.com.
authors.forename: Xiao-Qiu
authors.initials: XQ
authors.lastname: Zhou
mesh_terms: D000821:Animal Feed / Q000032:analysis; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002347:Carps / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004032:Diet / Q000662:veterinary; D019587:Dietary Supplements; D029941:Fish Proteins / Q000235:genetics* / Q000378:metabolism; D018928:Immunity, Mucosal / Q000276:immunology*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009525:Niacin / Q000172:deficiency*; D017422:Sequence Analysis, DNA / Q000662:veterinary; D015398:Signal Transduction / Q000187:drug effects; D062725:Tight Junction Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016207:Cytokines; D029941:Fish Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; D062725:Tight Junction Proteins; D009525:Niacin
keywords: Antioxidant capability; Grass carp; Intestine; Mucosal immune; Niacin; Tight junction protein; mRNA level