Enhancing lipophagy, a novel lipid catabolic pathway, for healthy and sustainable Atlantic salmon aquaculture (RD204)

Project Summary:

In salmon, excess fat from food is stored inside special cells called adipocytes. Under homeostasis, excess fat is broken down into usable fragments (free fatty acids, FFAs) by a recycling machinery in adipocytes known as ‘lipophagy’. These free fatty acids move to the mitochondria in the muscle for energy production, which keeps the organism active and healthy. However, this mechanism is dysregulated in the presence of excess fat.

In recent years, for sustainable salmon diet, fish oil based ingredients in the feed are replaced with vegetable oil based ingredients. Vegetable oil based feed is richer in the n-6 (pro-inflammatory) but lack n-3 fatty acids (anti-inflammatory). This feeding strategy comes at the expense of a marked increase in visceral fat deposition, reversal of polyunsaturated fatty acid (n-6/n-3) ratio, susceptibility to diseases and associated mortality in late stage salmon in marine farms, bringing significant economic losses to UK’s economy. Our pilot data provides a proof of concept that enhancing lipophagy in salmon cells significantly reduces the lipid overload, mobilise free fatty acids to mitochondria, maintains n-3/n-6 PUFA and reduces inflammation and atherogenesis.

In this full R& D proposal, we will take this innovation from proven concept in salmon cells through to validate in adult late stage salmon adipocytes and muscle in marine cages. We will also test rapamycin an established lipophagy inducer in Salmon feed. Success of Rapamycin in salmon feed will be a prototype setup for testing novel lipophagy inducers (e.g. Sulforaphane and Spermidine) as potential feed supplements in salmon diet.

This project will validate the process of enhancing lipophagy in salmon cells through the provision of a prototype feed supplement to improve farmed salmon health and reduce economic losses to the aquaculture industry.