Gene expression patterns indicate that a high-fat-high-carbohydrate diet causes mitochondrial dysfunction in fish

Expensive and unsustainable fishmeal is increasingly being replaced with cheaper lipids and carbohydrates as sources of energy in aquaculture. Although it is known that the excess of lipids and carbohydrates has negative effects on nutrient utilization, growth, metabolic homeostasis, and health of fish, our current understanding of mechanisms behind these effects is limited. To improve the understanding of diet-induced metabolic disorders (both in fish and other vertebrates), we conducted an eight-week high-fat-high-carbohydrate diet feeding trial on blunt snout bream (Megalobrama amblycephala), and studied gene expression changes (transcriptome and qPCR) in the liver. Disproportionately large numbers of differentially expressed genes were associated with mitochondrial metabolism, neurodegenerative diseases (Alzheimer's, Huntington's, and Parkinson's), and functional categories indicative of liver dysfunction. A high-fat-high-carbohydrate diet may have caused mitochondrial dysfunction, and possibly downregulated the mitochondrial biogenesis in the liver. While the relationship between diet and neurodegenerative disorders is well-established in mammals, this is the first report of this connection in fish. We propose that fishes should be further explored as a potentially promising model to study the mechanisms of diet-associated neurodegenerative disorders in humans.