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

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 while diets high in fat decrease DNL. The enzymes in the core DNL pathway have been well characterized; 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 semipurified high starch or high-fat diet. Both semipurified 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 nonpurified chow diet to either of the semipurified 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 that metabolic remodeling of the liver occurs rapidly in response to differing dietary components. Together, these findings highlight novel proteins associated with hepatic DNL independently of liver fat content and suggest rapid liver metabolic remodeling in response to dietary composition changes.