Metabolic fuel selection in rainbow trout: coping with intralipid infusion

The impact of hyperlipidemia on fuel selection has never been investigated in fish. This study quantifies how intralipid administration affects i) in vivo mobilization of lipids (lipolytic rate: R_a glycerol) and carbohydrates (hepatic glucose production: R_a glucose) in rainbow trout and ii) key proteins involved in the regulation of fuel metabolism that could explain changes in glycerol and glucose kinetics. Results show that intralipid triples lipolytic rate (from 2.5 ± 0.5 to 7.8 ± 1.1 µmol glycerol kg^-1·min^-1) and inhibits glucose production by 36% (from 7.3 ± 0.9 to 4.7 ± 0.4 µmol kg^-1·min^-1). The stimulation of lipolysis is probably driven by lipase activation (gene expression of hormone-sensitive lipase increases in muscle) or by mass action effect. Such a strong lipolytic response is quite surprising because baseline R_a glycerol is already particularly high in fish and is well known for its stability under a variety of stresses that have important effects in mammals. The reduction in trout R_a glucose is likely caused by a large decrease in glycogen mobilization because hepatic gluconeogenic pathway capacity may rise as a consequence of increases in gluconeogenesis gene transcript levels. In contrast to humans, which maintain steady glucose production in response to intralipid infusion, rainbow trout appears to overcompensate increased gluconeogenic capacity with a disproportionately large inhibition of glycogen breakdown. Overall, these intralipid-driven changes in glycerol and glucose kinetics allow fish to decrease their reliance on carbohydrates and amino acids by replacing them, in part, with fatty acids as metabolic fuels.NEW & NOTEWORTHY How do fish respond to an intralipid infusion (a soybean-derived emulsion used for parenteral nutrition of human patients)? In rainbow trout, intralipid administration triples the rate of lipid mobilization (lipolysis) and reduces hepatic glucose production by 36%. These changes in substrate fluxes allow fish to decrease their reliance on amino acids and carbohydrates by substituting them with fatty acids as metabolic fuels.