Linking Animal and Human Health: Researchers at NSAC Unravel Molecular Mechanisms of Fatty Liver Disease in Mink

Researchers at NSAC have discovered new pathophysiological mechanisms that contribute to the progression of fatty liver disease in mink, a strict carnivore. They report the first evidence for de novo lipid synthesis in mink with fatty liver based on the elevated gene expression of key enzymes of the fat synthesis pathway and the associated fatty acids. These findings demonstrate the rapidity and severity of the development of fatty liver during body weight loss. The Carnivore Nutrition and Physiology team making this discovery is lead by Dr. Kirsti Rouvinen-Watt and includes research assistant Lora Harris, recent NSAC M.Sc. graduates Morag Dick and Catherine Pal, and Sha Lei, a visiting Ph.D. student from China, together with their Finnish collaborators Dr. Petteri Nieminen and Dr. Anne-Mari Mustonen. Results of this research are reported in the British Journal of Nutrition.

Fatty liver (hepatic lipidosis or liver steatosis) may develop due to several causes. Of these, lifestyle related factors such as high intake of fat in the diet, and rapid mobilization of body fat during weight loss commonly lead to the development of fatty liver. The research team at NSAC, using the mink as model animal, have shown that while the initial accumulation of liver fat is a result of release of fatty acids from the (visceral) fat depots, the liver also makes new (de novo) fat which further increases the liver lipid load. Following the initial accumulation of excess fat in the liver cells, an adipogenic transformation of the liver tissue takes place. As a result, the liver begins to turn on genes that are normally expressed in the fatty (adipose) tissue and begins to produce more fat. This increases the severity of fatty liver disease in two ways; firstly by further increasing the amount of fat within the liver, but very importantly it may also inhibit the oxidation (burning) of fat for energy purposes. The NSAC team is already investigating if the activated fat synthesis pathway is interfering with the liver's ability to oxidize fatty acids.

Mink are at risk of developing fatty liver several times in their production cycle: during the fall when they deposit body fat in preparation for winter, during winter when slimming down in preparation for breeding, and again during lactation when fat is mobilized for milk production for the young. Better understanding of the disease mechanisms at the cellular and molecular levels will help researchers identify targets for effective ways of preventing or treating the development of fatty liver.

The results of this research will be very useful to the agricultural sector in Nova Scotia as mink is currently the number one agricultural export from the province, bringing in over 100 million dollars in revenue annually. Understanding of the pathophysiology of fatty liver development is also highly beneficial to the human health sector as the incidence of non-alcoholic fatty liver disease is rapidly increasing together with the associated metabolic syndrome, obesity and type 2 diabetes.

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