Liver proteomic assessment of mice fed high carbohydrate and high fat diets identify a disconnect between proteins associated with de novo lipogenesis and fat

ABSTRACT: De novo lipogenesis (DNL) has been implicated in the development and progression of hepatic liver steatosis. Hepatic DNL is strongly influenced by dietary macronutrient composition with diets high in carbohydrate increasing DNL and diets high in fat decreasing DNL. The enzymes in the core DNL pathway have been well characterised however less is known about proteins that play accessory or regulatory roles in DNL. In the current study, we associate measured rates of hepatic DNL and liver fat content with abundance of liver proteins from liquid chromatography mass spectrometry in mice to identify known and uncharacterised proteins that may have a role in DNL. Male C57BL/6J mice were fed either a standard chow diet a semi-purified high starch diet or a high fat diet. Both semi-purified diets resulted in increased body weight, fat mass and liver triglyceride content compared to chow-fed mice while hepatic DNL was increased in the high starch fed mice and decreased in the high fat fed mice. Proteomic analysis was carried out on the livers of these mice and proteins were identified that associated with either the rate of DNL or triglyceride content in the liver. There was no overlap between DNL and triglyceride associated proteins. We identify novel proteins associated with DNL that are involved in taurine metabolism, which suggests a link between these pathways. Further analysis identified proteins that are differentially regulated when comparing a non-purified chow diet to either of the semi-purified diets to provide a set of proteins that are regulated by the degree of dietary complexity alone. Finally, we compared the liver proteome between 4 week-fed and 30-week diet-fed mice and found remarkable similarity suggesting that the majority of diet-regulated proteins change early in response to differing dietary components.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Mark Larance  

LAB HEAD: Mark Larance

PROVIDER: PXD054323 | Pride | 2024-10-30

REPOSITORIES: Pride