Liver proteomics identifies a disconnect between proteins associated with de novo lipogenesis and triglyceride storage.

Abstract

De novo lipogenesis (DNL) has been implicated in the development and progression of liver steatosis. Hepatic DNL is strongly influenced by dietary macronutrient composition with diets high in carbohydrate increasing DNL and while diets high in fat decrease DNL. The enzymes in the core DNL pathway have been well characterised, however less is known about other liver proteins that play accessory or regulatory roles. In the current study, we associate measured rates of hepatic DNL and fat content with liver proteomic analysis in mice to identify known and unknown proteins that may have a role in DNL. Male mice were fed either a standard chow diet, a semi-purified high starch or high fat diet. Both semi-purified diets resulted in increased body weight, fat mass and liver triglyceride content compared to chow controls and hepatic DNL was increased in the high starch and decreased in high fat fed mice. Proteomic analysis identified novel proteins associated with DNL that are involved in taurine metabolism, suggesting a link between these pathways. There was no relationship between proteins that associated with DNL and those associated with liver triglyceride content. Further analysis identified proteins that are differentially regulated when comparing a non-purified chow diet to either of the semi-purified diets which provide a set of proteins that are influenced by dietary complexity. Finally, we compared the liver proteome between 4- and 30-week diet-fed mice and found remarkable similarity suggesting metabolic remodelling of the liver occurs rapidly in response to differing dietary components.