Programming effects of high-carbohydrate feeding of larvae on adult glucose metabolism in zebrafish,Danio rerio

Abstract

The aim of the present study was to determine the potential long-term metabolic effects of early nutritional programming on carbohydrate utilisation in adult zebrafish (Danio rerio). High-carbohydrate diets were fed to fish during four ontogenetic stages: from the firstfeeding stage to the end of the yolk-sac larval stage; from the first-feeding stage to 2 d after yolk-sac exhaustion; after yolk-sac exhaustion for 3 or 5 d. The carbohydrate stimuli significantly increased the body weight of the first-feeding groups in the short term. The expression of genes was differentially regulated by the early dietary intervention. The high-carbohydrate diets resulted in decreased plasma glucose levels in the adult fish. The mRNA levels and enzyme activities of glucokinase, pyruvate kinase, a-amylase and sodium-dependent glucose co-transporter 1 were up-regulated in the first-feeding groups. There was no significant change in the mRNA levels of glucose-6-phosphatase (G6Pase) in any experimental group, and the activity of G6Pase enzyme in the FF-5 (first feeding to 2 d after yolk-sac exhaustion) group was significantly different from that of the other groups. The expression of phosphoenolpyruvate carboxykinase gene in all the groups was significantly decreased. In the examined early programming range, growth performance was not affected. Taken together, data reported herein indicate that the period ranging from the polyculture to the external feeding stage is an important window for potential modification of the long-term physiological functions. In conclusion, the present study demonstrates that it is possible to permanently modify carbohydrate digestion, transport and metabolism of adult zebrafish through early nutritional programming.Key words: First feeding: Early nutritional programming: Carbohydrate diets: Glucose metabolism: ZebrafishThe use of carbohydrates as digestible energy sources in fish diets bears economic significance in aquaculture industry (1) .Diets that contain digestible carbohydrates can promote rapid growth and provide metabolic intermediates for the synthesis of other biologically important compounds (2,3) . When carbohydrates are not provided in feedstuffs, more proteins are catabolised for energy and for the synthesis of glucose, which impairs protein retention and increases N excretion into the environment (1,4) . Therefore, it is important to provide an appropriate amount of carbohydrates in fish diets. However, the mechanisms of carbohydrate digestion, absorption and metabolism are different among different fish species; that is, omnivorous or herbivorous fish can utilise higher amounts of dietary carbohydrates and exhibit a greater degree of protein sparing (5 -7) , whereas carnivorous fish species have a relatively low ability to utilise carbohydrates (8) . The liver plays an important role in the coordination of whole-body metabolic functions in response to nutritional status. Specifically, in conjunction with the gastrointestinal tract, the liver plays a major role in glucose metabol...

High or low dietary carbohydrate:protein ratios during first-feeding affect glucose metabolism and intestinal microbiota in juvenile rainbow trout

“…altered hormonal levels, such as insulin) rather than a direct programming effect on the target genes. By contrast, the metabolic genes differentially expressed at the early stimulus stage (glucose metabolism: GK, G6Pase, FBPase and PEPCK; and protein metabolism: GDHs and SDH) were no longer differentially expressed in liver at the juvenile stage, as opposed to data from a recent study with zebrafish, which observed a long-term programming effect for some of these metabolic markers (Fang et al, 2014). Another interesting long-term result concerns the effect of the early feeding on the intestinal fungi, whose profiles, differently expressed in alevins, remained differently expressed in juveniles.…”

“…Indeed, the short-term regulation of these parameters of glucose metabolism was not observed in a previous study with trout alevins (Geurden et al, 2007), which may be related to the duration of the stimulus (5 days versus 3 days previously) or the type of carbohydrate intake (glucose and gelatinized starch versus dextrin previously). An effect of the duration of the first-feeding stimulus was also seen for zebrafish, in which the gluconeogenic genes G6Pase and PEPCK were, as in the present study, downregulated at the end of the 5-day stimulus, whereas the reverse was seen at the end of the 3-day stimulus (Fang et al, 2014). …”

“…We must note here the absence of regulation of genes involved in the transport of glucose, amino acids and small peptides (SGLT1, GLUTs, NBAT and PEPT1) and in carbohydrate digestion (amylase and maltase). The latter was unexpected as the hyperglucidic diet contained a source of complex carbohydrates requiring digestive breakdown (gelatinized starch) and as digestive enzyme expression was highly upregulated after an early 3-day dextrin stimulus in studies with both trout (Geurden et al, 2007) and with zebrafish (Fang et al, 2014). On the whole, the present short-term feeding stimulus showed that the use of digestible starch and glucose has an immediate and drastic effect on intermediary metabolism at a molecular level in trout alevins.…”

“…Possible biological mechanisms for 'imprinting' the nutritional event until adulthood in mammalian vertebrates comprise adaptive changes in gene expression pattern or cellular phenotype (epigenetic phenomenon), nutrient-sensitive signalling pathways and adaptive clonal selection, which may be transmitted to future offspring (Lucas, 1998;Symonds et al, 2009;Waterland and Jirtle, 2003;Gut and Verdin, 2013). Experimental data on the concept of nutritional programming in fish are limited and some first knowledge stems from recent studies dealing with the possibility of altering the functioning of long-chain fatty acid desaturation in European seabass (Dicentrarchus labrax) (Vagner et al, 2007;Vagner et al, 2009), the use of dietary carbohydrates in rainbow trout [Oncorhynchus mykiss (Walbaum 1792)] (Geurden et al, 2007) or zebrafish (Danio rerio) (Fang et al, 2014;Rocha et al, 2014) and the acceptance and use of plant-based feed in rainbow trout . Taken together, the results all showed particular long-term effects on molecular markers or on growth, because of the acute early-life exposure to the imposed nutritional stimulus.…”

“…gluconeogenesis, glycolysis) was altered by the early stimulus in the trout, even not in the short term, which we hypothesized to be due its short duration (only 3 days) or to the carbohydrate source (dextrin). In contrast, and following an experimental procedure similar to the one applied in rainbow trout (Geurden et al, 2007), a recent study with zebrafish revealed long-lasting changes in the expression of genes involved in glucose intestinal transport and in glucose metabolism (Fang et al, 2014). As it is uncertain whether this difference in response is species-related (omnivorous feeding habit as well as faster larval development and higher rearing temperature in zebrafish compared with trout), we decided to boost the early stimulus in the present study with rainbow trout.…”