Email updates

Keep up to date with the latest news and content from BMC Genomics and BioMed Central.

Open Access Research article

Metabolic consequences of microRNA-122 inhibition in rainbow trout, Oncorhynchus mykiss

Jan A Mennigen1, Christopher J Martyniuk2, Iban Seiliez1, Stéphane Panserat1 and Sandrine Skiba-Cassy1*

Author Affiliations

1 Institut National de la Recherche Agronomique (INRA), Nutrition, Metabolism and Aquaculture Unit (UR1067), Saint-Pée-sur-Nivelle F-64310, France

2 Canadian Rivers Institute and Department of Biology, University of New Brunswick, Saint John, NB E2L 4 L5, Canada

For all author emails, please log on.

BMC Genomics 2014, 15:70  doi:10.1186/1471-2164-15-70

Published: 27 January 2014

Abstract

Background

MicroRNAs (miRNAs) are small regulatory molecules which post-transcriptionally regulate mRNA stability and translation. Several microRNAs have received attention due to their role as key metabolic regulators. In spite of the high evolutionary conservation of several miRNAs, the role of miRNAs in lower taxa of vertebrates has not been studied with regard to metabolism. The liver-specific and highly abundant miRNA-122 is one of the most widely studied miRNA in mammals, where it has been implicated in the control of hepatic lipid metabolism. Following our identification of acute postprandial, nutritional and endocrine regulation of hepatic miRNA-122 isomiRNA expression in rainbow trout, we used complementary in silico and in vivo approaches to study the role of miRNA-122 in rainbow trout metabolism. We hypothesized that the role of miRNA-122 in regulating lipid metabolism in rainbow trout is conserved to that in mammals and that modulation of miRNA-122 function would result in altered lipid homeostasis and secondarily altered glucose homeostasis, since lipogenesis has been suggested to act as glucose sink in trout.

Results

Our results show that miRNA-122 was functionally inhibited in vivo in the liver. Postprandial glucose concentrations increased significantly in rainbow trout injected with a miRNA-122 inhibitor, and this effect correlated with decreases in hepatic FAS protein abundance, indicative of altered lipogenic potential. Additionally, miRNA-122 inhibition resulted in a 20% decrease in plasma cholesterol concentration, an effect associated with increased expression of genes involved in cholesterol degradation and excretion.

Conclusions

Overall evidence suggests that miRNA-122 may have evolved in early vertebrates to support liver-specific metabolic functions. Nevertheless, our data also indicate that metabolic consequences of miRNA-122 inhibition may differ quantitatively between vertebrate species and that distinct direct molecular targets of miRNA-122 may mediate metabolic effects between vertebrate species, indicating that miRNA-122 - mRNA target relationships may have undergone species-specific evolutionary changes.

Keywords:
Glycolysis; Lipogenesis; MicroRNA; Fish; Metabolism; Gene expression; Insulin signaling