Risk of Feed Additives in High-lipid Fish Diets: Effects of Propionate and Docosahexaenoic Acid on Liver and Intestinal Health in Zebrafish (Danio rerio Hamilton-Buchanan, 1822)
Doctoral thesis
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Date
2022Metadata
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- Institutt for biologi [2594]
Abstract
The use of high-fat diets (HFDs) is a common practice employed to improve growth and feed efficiency in aquaculture. Propionic acid and its sodium salt are widely used in Asian fish feeds as a safe inhibitor of mold growth, and as a growth-promoting and immune-enhancing feed additive. Docosahexaenoic acid (DHA, 22:6n-3) is known as an n-3 long-chain polyunsaturated fatty acid that has well-known accepted beneficial effects. However, most current knowledge on the effects of propionate and DHA comes from trials using standard low-fat diets. Therefore, this work aims to explore the effects of HFD feeding on the health of zebrafish (Danio rerio) and how this condition is affected by propionate and DHA.
Both the liver and intestine of zebrafish were subjected to changes in lipid metabolism, pro-oxidative status, and protein propionylation upon HFD feeding. In this work, propionate led to intestinal damage in the context of HFD. It induced intestinal oxidative stress via superoxide dismutase 2 propionylation. Moreover, intestinal oxidative stress resulting from superoxide dismutase 2 propionylation contributed to compositional changes in gut microbiota. This altered gut microbiota in turn compromised fish health. Besides, low level of DHA supplementation (0.5%) alleviated HFD-induced hepatic steatosis, while high level of DHA supplementation (2.0%) induced liver injury in the context of HFD. The suppression of the cyclin d1-cyclin-dependent kinase 4 pathway and increased gut microbiota-mediated fatty acid β-oxidation contributed to the hepatic lipid-lowering effect of 0.5% DHA. However, lipid peroxidation-activated mitochondrial apoptosis and lipopolysaccharide-stimulated death receptor pathways mediated the liver injury induced by 2.0% DHA. This work will enable better understanding of the interactions between HFD and feed additives such as propionate and DHA in diets for zebrafish. Also, these findings should be taken into consideration when using propionate and DHA in high-lipid formulations of other farmed fish species.