The Growth-Promoting Effect of Dietary Nucleotides in Fish Is Associated with an Intestinal Microbiota-Mediated Reduction in Energy Expenditure

J Nutr. 2017 May;147(5):781-788. doi: 10.3945/jn.116.245506. Epub 2017 Mar 29.

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 and fiaf were 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 of fiaf than 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% lower fiaf expression 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 and 2) reduced FA oxidation associated with increased microbial suppression of intestinal fiaf.

Keywords: Fiaf; inflammation; microbiota; nucleotides; standard metabolic rate.

MeSH terms

  • Angiopoietin-Like Protein 4
  • Angiopoietins / metabolism
  • Animal Husbandry
  • Animal Nutritional Physiological Phenomena
  • Animals
  • Basal Metabolism / drug effects*
  • Cytokines / metabolism
  • Dietary Supplements*
  • Gastrointestinal Microbiome*
  • Inflammation / metabolism
  • Intestinal Mucosa / metabolism
  • Intestines / drug effects*
  • Intestines / microbiology
  • Kidney / drug effects
  • Kidney / metabolism
  • Lipolysis / genetics
  • Liver / drug effects
  • Liver / enzymology
  • Muscles / drug effects
  • Muscles / enzymology
  • Nucleotides / pharmacology*
  • Oxygen Consumption
  • Rest
  • Zebrafish Proteins / metabolism
  • Zebrafish* / metabolism
  • Zebrafish* / microbiology

Substances

  • Angiopoietin-Like Protein 4
  • Angiopoietins
  • Angptl4 protein, zebrafish
  • Cytokines
  • Nucleotides
  • Zebrafish Proteins