title: The Growth-Promoting Effect of Dietary Nucleotides in Fish Is Associated with an Intestinal Microbiota-Mediated Reduction in Energy Expenditure.
abstract: Background:Nucleotides have been used as functional nutrients to improve the growth and health of animals, including fish. The mechanism involved in the growth-promotion effect of nucleotides is still unclear.Objective:We investigated the bioenergetic mechanism underlying the growth-promotion effect of nucleotides in zebrafish and the associated roles played by the intestinal microbiota.Methods:Larval zebrafish were fed a control or a 0.1% mixed nucleotides-supplemented diet for 2 wk. Standard metabolic rate, the minimal rate of energy expenditure by animals at rest, was evaluated by oxygen consumption with the use of a respirometer. The expressions of fasting-induced adipose factor (Fiaf), inflammatory cytokines, and genes involved in fatty acid (FA) oxidation were tested by quantitative reverse transcriptase-polymerase chain reaction. The intestinal microbiota from the nucleotide-fed fish (NT fish) or control fish was transferred to 3-d postfertilization germ-free zebrafish in which oxygen consumption and expression of cytokines andfiafwere evaluated.Results:Compared with controls, nucleotide supplementation at 0.1% increased the weight and energy gains of zebrafish by 10% and 25%, respectively (P< 0.01). Standard metabolic rate was 28% lower in NT fish than in controls (P< 0.001). Nucleotide supplementation downregulated the inflammatory tone in the head kidney of the fish. Moreover, NT fish had a 51% lower intestinal expression offiafthan did controls (P< 0.05), which was consistent with decreased expression of key genes involved in FA oxidation [carnitine:palmitoyl transferase 1a (cpt1a) and medium-chain acyl coenzyme A dehydrogenase (mcad)] in liver and muscle. Germ-free zebrafish colonized with microbiota from NT fish had a 25% lower standard metabolic rate than did those colonized by control microbiota (P< 0.01), whereas direct nucleotide feeding of germ-free zebrafish did not affect standard metabolic rate relative to germ-free controls that were not fed nucleotides. Furthermore, germ-free zebrafish colonized with nucleotide microbiota exhibited downregulated inflammatory tone and 33% lowerfiafexpression compared with their control microbiota-colonized counterparts.Conclusions:The growth-promoting effect of dietary nucleotides in zebrafish involves 2 intestinal microbiota-mediated mechanisms that result in reduced standard metabolic rate:1) lower inflammatory tone and2) reduced FA oxidation associated with increased microbial suppression of intestinalfiaf.
authors.affiliation: Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China; and.|Jangxi Academy of Agricultural Sciences, Nanchang, Jiangxi, China.
authors.forename: Xiaoze
authors.initials: X
authors.lastname: Guo
authors.affiliation: Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China; and.
authors.forename: Chao
authors.initials: C
authors.lastname: Ran
authors.affiliation: Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China; and.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China; and.
authors.forename: Suxu
authors.initials: S
authors.lastname: He
authors.affiliation: Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China; and.
authors.forename: Min
authors.initials: M
authors.lastname: Jin
authors.affiliation: Key Laboratory for Feed Biotechnology of the Ministry of Agriculture, Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China; and zhou_zg@msn.com.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000378:metabolism; D000822:Animal Husbandry; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D001481:Basal Metabolism / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D019587:Dietary Supplements; D000069196:Gastrointestinal Microbiome; D007249:Inflammation / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000382:microbiology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008066:Lipolysis / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D009132:Muscles / Q000187:drug effects / Q000201:enzymology; D009711:Nucleotides / Q000494:pharmacology*; D010101:Oxygen Consumption; D012146:Rest; D015027:Zebrafish / Q000378:metabolism / Q000382:microbiology; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; C574690:Angptl4 protein, zebrafish; D016207:Cytokines; D009711:Nucleotides; D029961:Zebrafish Proteins
keywords: Fiaf; inflammation; microbiota; nucleotides; standard metabolic rate